Abstract
Arsenical medicine has obtained its status in traditional Chinese medicine for more than 2,000 years. In the 1970s, arsenic trioxide was identified to have high efficacy and potency for the treatment of acute promyelocytic leukemia, which promoted many studies on the therapeutic effects of arsenic trioxide. Currently, arsenic trioxide is widely used to treat acute promyelocytic leukemia and various solid tumors through various mechanisms of action in clinical practice; however, it is accompanied by a series of adverse reactions, especially cardiac toxicity. This review presents a comprehensive overview of arsenic trioxide from preclinical and clinical efficacy, potential mechanisms of action, toxicities, and rescue strategies for toxicities to provide guidance or assistance for the clinical application of arsenic trioxide.
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References
Abele M, Muller SL, Schleicher S, Hartmann U, Doring M, Queudeville M, Lang P, Handgretinger R, Ebinger M (2021) Arsenic trioxide in pediatric cancer—a case series and review of literature. Pediatr Hematol Oncol 38(5):471–485. https://doi.org/10.1080/08880018.2021.1872748
Ahn RW, Chen F, Chen H, Stern ST, Clogston JD, Patri AK, Raja MR, Swindell EP, Parimi V, Cryns VL, O’Halloran TV (2010) A novel nanoparticulate formulation of arsenic trioxide with enhanced therapeutic efficacy in a murine model of breast cancer. Clin Cancer Res 16(14):3607–3617. https://doi.org/10.1158/1078-0432.Ccr-10-0068
Akhtar A, Ghali L, Wang SX, Bell C, Li D, Wen X (2019) Optimisation of folate-mediated liposomal encapsulated arsenic trioxide for treating HPV-positive cervical cancer cells in vitro. Int J Mol Sci 20(9):2156. https://doi.org/10.3390/ijms20092156
Aldoss I, Mark L, Vrona J, Ramezani L, Weitz I, Mohrbacher AM, Douer D (2014) Adding ascorbic acid to arsenic trioxide produces limited benefit in patients with acute myeloid leukemia excluding acute promyelocytic leukemia. Ann Hematol 93(11):1839–1843. https://doi.org/10.1007/s00277-014-2124-y
Amini-Khoei H, Hosseini MJ, Momeny M, Rahimi-Balaei M, Amiri S, Haj-Mirzaian A, Khedri M, Jahanabadi S, Mohammadi-Asl A, Mehr SE, Dehpour AR (2016) Morphine attenuated the cytotoxicity induced by arsenic trioxide in H9c2 cardiomyocytes. Biol Trace Elem Res 173(1):132–139. https://doi.org/10.1007/s12011-016-0631-5
An K, Xue MJ, Zhong JY, Yu SN, Lan TS, Qi ZQ, Xia JJ (2020) Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice by inducing CD4(+) T cell apoptosis. J Neuroinflammation 17(1):147. https://doi.org/10.1186/s12974-020-01829-x
Ardalan B, Subbarayan PR, Ramos Y, Gonzalez M, Fernandez A, Mezentsev D, Reis I, Duncan R, Podolsky L, Lee K, Lima M, Ganjei-Azar P (2010) A phase I study of 5-fluorouracil/leucovorin and arsenic trioxide for patients with refractory/relapsed colorectal carcinoma. Clin Cancer Res 16(11):3019–3027. https://doi.org/10.1158/1078-0432.CCR-09-2590
Au W-Y, Kwong Y-L (2005) Frequent varicella zoster reactivation associated with therapeutic use of arsenic trioxide: portents of an old scourge. J Am Acad Dermatol 53(5):890–892
Au W-Y, Kwong Y-L (2008) Arsenic trioxide: safety issues and their management. Acta Pharmacol Sin 29(3):296–304. https://doi.org/10.1111/j.1745-7254.2008.00771.x
Au WY, Kumana CR, Kou M, Mak R, Chan GCF, Lam CW, Kwong YL (2003) Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia. Blood 102(1):407–408. https://doi.org/10.1182/blood-2003-01-0298
Bao Z, Han Z, Zhang B, Yu Y, Xu Z, Ma W, Ding F, Zhang L, Yu M, Liu S, Jin M, Yan G, Huang Q, Wang X, Hua B, Yang F, Li Y, Liu Y, Zagidullin N, Carvalho K, Li B, Wang N, Cai B (2019) Arsenic trioxide blocked proliferation and cardiomyocyte differentiation of human induced pluripotent stem cells: Implication in cardiac developmental toxicity. Toxicol Lett 309:51–58. https://doi.org/10.1016/j.toxlet.2019.03.008
Barbey JT, Pezzullo JC, Soignet SL (2003) Effect of arsenic trioxide on QT interval in patients with advanced malignancies. J Clin Oncol 21(19):3609–3615. https://doi.org/10.1200/jco.2003.10.009
Baysan A, Yel L, Gollapudi S, Su H, Gupta S (2007) Arsenic trioxide induces apoptosis via the mitochondrial pathway by upregulating the expression of Bax and Bim in human B cells. Int J Oncol 30(2):313–318
Bessho M, Aki T, Funakoshi T, Unuma K, Noritake K, Kato C, Uemura K (2013) Rho-kinase inhibitor Y-27632 attenuates arsenic trioxide toxicity in H9c2 cardiomyoblastoma cells. Cardiovasc Toxicol 13(3):267–277. https://doi.org/10.1007/s12012-013-9206-2
Binu P, Gifty K, Vineetha RC, Abhilash S, Arathi P, Nair RH (2018) Eugenol, a plant-derived phenolic nutraceutical, protects thiol (SH) group in myocardium from ROS-mediated oxidation under chemotherapeutic stress induced by arsenic trioxide—a in vivo model study. Drug Chem Toxicol 41(3):352–357. https://doi.org/10.1080/01480545.2018.1424179
Binu P, Priya N, Abhilash S, Vineetha RC, Nair RH (2017) Studies on curative efficacy of monoterpene eugenol on anti-leukemic drug arsenic trioxide induced cardiotoxicity. Biomed Pharmacother 91:559–566. https://doi.org/10.1016/j.biopha.2017.04.087
Bobe P, Bonardelle D, Benihoud K, Opolon P, Chelbi-Alix MK (2006) Arsenic trioxide: A promising novel therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice. Blood 108(13):3967–3975. https://doi.org/10.1182/blood-2006-04-020610
Cai BZ, Meng FY, Zhu SL, Zhao J, Liu JQ, Liu CJ, Chen N, Ye ML, Li ZY, Ai J, Lu YJ, Yang BF (2010) Arsenic trioxide induces the apoptosis in bone marrow mesenchymal stem cells by intracellular calcium signal and caspase-3 pathways. Toxicol Lett 193(2):173–178. https://doi.org/10.1016/j.toxlet.2010.01.001
Camacho LH, Soignet SL, Chanel S, Ho R, Heller G, Scheinberg DA, Ellison R, Warrell RP Jr (2000) Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide. J Clin Oncol 18(13):2620–2625. https://doi.org/10.1200/jco.2000.18.13.2620
Cha Y, Park DW, Lee CH, Baek SH, Kim SY, Kim JR, Kim JH (2006) Arsenic trioxide induces apoptosis in human colorectal adenocarcinoma HT-29 cells through ROS. Cancer Res Treat 38(1):54–60. https://doi.org/10.4143/crt.2006.38.1.54
Chang KJ, Yang MH, Zheng JC, Li B, Nie W (2016) Arsenic trioxide inhibits cancer stem-like cells via down-regulation of Gli1 in lung cancer. Am J Transl Res 8(2):1133–1143
Chaudhary A, Bhardwaj SK, Khan A, Srivastava A, Sinha KK, Ali M, Haque R (2023) Combinatorial effect of arsenic and herbal compounds in telomerase-mediated apoptosis induction in liver cancer. Biol Trace Elem Res 201(7):3300–3310. https://doi.org/10.1007/s12011-022-03430-0
Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z (1996) In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 88(3):1052–1061
Chen J, Chen S, Luo H, Wu W, Wang S (2023) The application of arsenic trioxide in cancer: An umbrella review of meta-analyses based on randomized controlled trials. J Ethnopharmacol 316:116734. https://doi.org/10.1016/j.jep.2023.116734
Chen S, Wu JL, Liang Y, Tang YG, Song HX, Wu LL, Xing YF, Yan N, Li YT, Wang ZY, Xiao SJ, Lu X, Chen SJ, Lu M (2021) Arsenic trioxide rescues structural p53 mutations through a cryptic allosteric site. Cancer Cell 39(2):225–+.https://doi.org/10.1016/j.ccell.2020.11.013
Chen X, Huang Y, Chen H, Chen Z, Chen J, Wang H, Li D, Su Z (2022) Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression. J Nanobiotechnology 20(1):34. https://doi.org/10.1186/s12951-021-01161-3
Chen X, Jiang Y, Zeng T, Li JJ, Erfm, sciences (2020) Overexpression of the long noncoding RNA NEAT1 protects against As2O3-induced injury of cardiomyocyte by inhibiting the miR-124/NF-κB signaling pathway. Eur Rev Med Pharmacol Sci 24(3):1378–1390. https://doi.org/10.26355/eurrev_202002_20195
Chen YC, Lin-Shiau SY, Lin JK (1998) Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis. J Cell Physiol 177(2):324–333. https://doi.org/10.1002/(SICI)1097-4652(199811)177:2%3c324::AID-JCP14%3e3.0.CO;2-9
Chene C, Rongvaux-Gaida D, Thomas M, Rieger F, Nicco C, Batteux F (2023) Optimal combination of arsenic trioxide and copper ions to prevent autoimmunity in a murine HOCl-induced model of systemic sclerosis. Front Immunol 14:1149869. https://doi.org/10.3389/fimmu.2023.1149869
Chiu CY, Chung MN, Lan KC, Yang RS, Liu SH (2020) Exposure of low-concentration arsenic induces myotube atrophy by inhibiting an Akt signaling pathway. Toxicol in Vitro 65:104829. https://doi.org/10.1016/j.tiv.2020.104829
Chou WC, Chen HY, Yu SL, Cheng L, Yang PC, Dang CV (2005) Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood 106(1):304–310. https://doi.org/10.1182/blood-2005-01-0241
Chu W, Li C, Qu X, Zhao D, Wang X, Yu X, Cai F, Liang H, Zhang Y, Zhao X, Li B, Qiao G, Dong D, Lu Y, Du Z, Yang B (2012) Arsenic-induced interstitial myocardial fibrosis reveals a new insight into drug-induced long QT syndrome. Cardiovasc Res 96(1):90–98. https://doi.org/10.1093/cvr/cvs230
Citarella A, Catanzaro G, Besharat ZM, Trocchianesi S, Barbagallo F, Gosti G, Leonetti M, Di Fiore A, Coppola L, Autilio TM, Spinello Z, Vacca A, De Smaele E, Venneri MA, Ferretti E, Masuelli L, Po A (2023) Hedgehog-GLI and notch pathways sustain chemoresistance and invasiveness in colorectal cancer and their inhibition restores chemotherapy efficacy. Cancers (Basel) 15(5):1471. https://doi.org/10.3390/cancers15051471
Dagher T, Maslah N, Edmond V, Cassinat B, Vainchenker W, Giraudier S, Pasquier F, Verger E, Niwa-Kawakita M, Lallemand-Breitenbach V, Plo I, Kiladjian J-J, Villeval J-L, de Thé H (2021) JAK2V617F myeloproliferative neoplasm eradication by a novel interferon/arsenic therapy involves PML. J Exp Med 218(2):20201268. https://doi.org/10.1084/jem.20201268
de The H, Pandolfi PP, Chen Z (2017) Acute promyelocytic leukemia: a paradigm for oncoprotein-targeted cure. Cancer Cell 32(5):552–560. https://doi.org/10.1016/j.ccell.2017.10.002
Deng Y, Lin C, Zheng J, Fu M, Liang X, Chen J, Xiao P, Wu M (2000) Overexpression of Bcl-2 partly inhibits apoptosis of human cervical cancer SiHa cells induced by arsenic trioxide. Chin Med J 113(1):84–88
Deng Y, Lin C, Zheng J, Liang X, Chen J, Fu M, Xiao P, Wu M (1999) Mechanisms of arsenic trioxide induced apoptosis of human cervical cancer HeLa cells and protection by Bcl-2. Sci China Ser C 42(6):635–643. https://doi.org/10.1007/BF02881582
Dong S, Li Z, Kong J, Wu S, Gao J, Sun W (2022) Arsenic trioxide inhibits angiogenesis of hepatocellular carcinoma after insufficient radiofrequency ablation via blocking paracrine angiopoietin-1 and angiopoietin-2. Int J Hyperthermia 39(1):888–896. https://doi.org/10.1080/02656736.2022.2093995
Duan XH, Ju SG, Han XW, Ren JZ, Li FY, Chen PF, Wu YY, Li H (2020) Arsenic trioxide-eluting Callispheres beads is more effective and equally tolerant compared with arsenic trioxide/lipiodol emulsion in the transcatheter arterial chemoembolization treatment for unresectable hepatocellular carcinoma patients. Eur Rev Med Pharmacol Sci 24(3):1468–1480. https://doi.org/10.26355/eurrev_202002_20206
Eguchi R, Fujimori Y, Takeda H, Tabata C, Ohta T, Kuribayashi K, Fukuoka K, Nakano T (2011) Arsenic trioxide induces apoptosis through JNK and ERK in human mesothelioma cells. J Cell Physiol 226(3):762–768. https://doi.org/10.1002/jcp.22397
El Hajj H, Hleihel R, El Sabban M, Bruneau J, Zaatari G, Cheminant M, Marcais A, Akkouche A, Hasegawa H, Hall W, De The H, Hermine O, Bazarbachi A (2021) Loss of interleukin-10 activates innate immunity to eradicate adult T-cell leukemia-initiating cells. Haematologica 106(5):1443–1456. https://doi.org/10.3324/haematol.2020.264523
Fan Y, Wang C, Zhang Y, Hang P, Liu Y, Pan Z, Wang N, Du Z (2013) Genistein ameliorates adverse cardiac effects induced by arsenic trioxide through preventing cardiomyocytes apoptosis. Cell Physiol Biochem 31(1):80–91. https://doi.org/10.1159/000343351
Fan Z, He J, Fu T, Zhang W, Yang G, Qu X, Liu R, Lv L, Wang J (2019a) Arsenic trioxide inhibits EMT in hepatocellular carcinoma by promoting lncRNA MEG3 via PKM2. Biochem Biophys Res Commun 513(4):834–840. https://doi.org/10.1016/j.bbrc.2019.04.081
Fan Z, He J, Fu T, Zhang W, Yang G, Qu X, Liu R, Lv L, Wang JJB, communications br (2019) Arsenic trioxide inhibits EMT in hepatocellular carcinoma by promoting lncRNA MEG3 via PKM2. Biochem Biophys Res Commun 513(4):834–840. https://doi.org/10.1016/j.bbrc.2019.04.081
Fang S, Wan X, Zou X, Sun S, Hao X, Liang C, Zhang Z, Zhang F, Sun B, Li H, Yu B (2021a) Arsenic trioxide induces macrophage autophagy and atheroprotection by regulating ROS-dependent TFEB nuclear translocation and AKT/mTOR pathway. Cell Death Dis 12(1):88. https://doi.org/10.1038/s41419-020-03357-1
Fang SH, Wan X, Zou XY, Sun S, Hao XR, Liang CC, Zhang ZM, Zhang FN, Sun B, Li HL, Yu B (2021b) Arsenic trioxide induces macrophage autophagy and atheroprotection by regulating ROS-dependent TFEB nuclear translocation and AKT/mTOR pathway. Cell Death Dis 12(1):18. https://doi.org/10.1038/s41419-020-03357-1
Fang Y, Zhang Z (2020) Arsenic trioxide as a novel anti-glioma drug: a review. Cell Mol Biol Lett 25:44. https://doi.org/10.1186/s11658-020-00236-7
Florea AM, Busselberg D (2008) Arsenic trioxide in environmentally and clinically relevant concentrations interacts with calcium homeostasis and induces cell type specific cell death in tumor and non-tumor cells. Toxicol Lett 179(1):34–42. https://doi.org/10.1016/j.toxlet.2008.03.019
Freyer CW, Peterson CE, Man Y, Przespolewski A, Baron J, Luger SM (2021) Herpes zoster during arsenic trioxide therapy for acute promyelocytic leukemia. Leuk Lymphoma 62(3):696–702. https://doi.org/10.1080/10428194.2020.1838507
Gan R, Liu H, Wu S, Huang R, Tang Z, Zhang N, Hu L (2023) Curcumin alleviates arsenic trioxide-induced inflammation and pyroptosis via the NF-kappaB/NLRP3 signaling pathway in the hypothalamus of ducks. Biol Trace Elem Res 201(5):2503–2511. https://doi.org/10.1007/s12011-022-03321-4
Gao J, Wang G, Wu J, Zuo Y, Zhang J, Chen J (2019) Arsenic trioxide inhibits Skp2 expression to increase chemosensitivity to gemcitabine in pancreatic cancer cells. Am J Transl Res 11(2):991–997
Gao L, Xue B, Xiang B, Liu KJ (2020a) Arsenic trioxide disturbs the LIS1/NDEL1/dynein microtubule dynamic complex by disrupting the CLIP170 zinc finger in head and neck cancer. Toxicol Appl Pharmacol 403:115158. https://doi.org/10.1016/j.taap.2020.115158
Gao L, Xue B, Xiang B, Liu KJ (2020) Arsenic trioxide disturbs the LIS1/NDEL1/dynein microtubule dynamic complex by disrupting the CLIP170 zinc finger in head and neck cancer. Toxicol Appl Pharmacol 403:115158. https://doi.org/10.1016/j.taap.2020.115158
Gautier EL, Huby T, Witztum JL, Ouzilleau B, Miller ER, Saint-Charles F, Aucouturier P, Chapman MJ, Lesnik P (2009) Macrophage apoptosis exerts divergent effects on atherogenesis as a function of lesion stage. Circulation 119(13):1795-U1186. https://doi.org/10.1161/circulationaha.108.806158
Ge QF, Ouyang GF, Chen Y, Zhang Y, Mu QT, Lu Y (2012) Effects of arsenic trioxide combined with bortezomib on apoptosis of multiple myeloma cell line KM3 and its mechanisms. Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = J Exp Hematol/J Assoc Pathophysiol. 20(1):112–115
George B, Mathews V, Poonkuzhali B, Shaji RV, Srivastava A, Chandy M (2004) Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience. Leukemia 18(10):1587–1590. https://doi.org/10.1038/sj.leu.2403480
Ghaffari SH, Momeny M, Bashash D, Mirzaei R, Ghavamzadeh A, Alimoghaddam K (2012) Cytotoxic effect of arsenic trioxide on acute promyelocytic leukemia cells through suppression of NFkbeta-dependent induction of hTERT due to down-regulation of Pin1 transcription. Hematology 17(4):198–206. https://doi.org/10.1179/1607845412Y.0000000008
Glass JL, Derkach A, Hilden P, King A, Seo SK, Ahr K, Kishtagari A, Levine RL, Tallman MS, Douer D (2021) Arsenic trioxide therapy predisposes to herpes zoster reactivation despite minimally myelosuppressive therapy. Leuk Res 106:106569. https://doi.org/10.1016/j.leukres.2021.106569
Goussetis DJ, Altman JK, Glaser H, McNeer JL, Tallman MS, Platanias LC (2010) Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide. J Biol Chem 285(39):29989–29997. https://doi.org/10.1074/jbc.M109.090530
Hamidou M, Neel A, Poupon J, Amoura Z, Ebbo M, Sibilia J, Viallard JF, Gaborit B, Volteau C, Hardouin JB, Hachulla E, Rieger F (2021) Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus erythematosus: an open-label phase IIa trial (Lupsenic). Arthritis Res Ther 23(1):70. https://doi.org/10.1186/s13075-021-02454-6
Han YH, Kim SZ, Kim SH, Park WH (2008) Suppression of arsenic trioxide-induced apoptosis in HeLa cells by N-acetylcysteine. Mol Cells 26(1):18–25
Hao L, Zhao J, Wang X, Wang H, Wang H, Xu G (2013) Hepatotoxicity from arsenic trioxide for pediatric acute promyelocytic leukemia. J Pediatr Hematol Oncol 35(2):e67-70. https://doi.org/10.1097/MPH.0b013e31827e91bc
Haybar H, Shahrabi S, Rezaeeyan H, Jodat H, Saki N (2019a) Strategies to inhibit arsenic trioxide-induced cardiotoxicity in acute promyelocytic leukemia. J Cell Physiol 234(9):14500–14506. https://doi.org/10.1002/jcp.28292
Haybar H, Shahrabi S, Rezaeeyan H, Jodat H, Saki N NJ, JJcop (2019) Strategies to inhibit arsenic trioxide-induced cardiotoxicity in acute promyelocytic leukemia. J Cell Physiol 234(9):1500–1506. https://doi.org/10.1002/jcp.28292
Held LA, Rizzieri D, Long GD, Gockerman JP, Diehl LF, de Castro CM, Moore JO, Horwitz ME, Chao NJ, Gasparetto C (2013) A Phase I study of arsenic trioxide (Trisenox), ascorbic acid, and bortezomib (Velcade) combination therapy in patients with relapsed/refractory multiple myeloma. Cancer Invest 31(3):172–176. https://doi.org/10.3109/07357907.2012.756109
Helso SN, Roug AS, Mork M, Maksten EF, Severinsen MT (2020) Severe peripheral neuropathy from treatment with arsenic trioxide in a patient suffering from acute promyelocytic leukemia. J Hematol 9(3):89–92. https://doi.org/10.14740/jh617
Hermine O, Herv, eacute, Dombret, Poupon J, Arnulf B, Lefr F, egrave, re, Rousselot P, Damaj G, Delarue R, Fermand JP, Brouet JC, Degos L, Varet B, Th Hd, eacute, Bazarbachi A (2004) Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma. Hematol J 5(2):130–134. https://doi.org/10.1038/sj.thj.6200374
Hernandez Dominguez O, Yilmaz S, Steele SR (2023) Stage IV colorectal cancer management and treatment. J Clin Med 12(5):2072. https://doi.org/10.3390/jcm12052072
Hofmann S, Mai J, Masser S, Groitl P, Herrmann A, Sternsdorf T, Brack-Werner R, Schreiner S (2020) ATO (arsenic trioxide) effects on promyelocytic leukemia nuclear bodies reveals antiviral intervention capacity. Adv Sci (Weinh) 7(8):1902130. https://doi.org/10.1002/advs.201902130
Hoonjan M, Jadhav V, Bhatt P (2018) Arsenic trioxide: insights into its evolution to an anticancer agent. J Biol Inorg Chem 23(3):313–329. https://doi.org/10.1007/s00775-018-1537-9
Hu HT, Yao QJ, Meng YL, Li HL, Zhang H, Luo JP, Guo CY, Geng X (2017) Arsenic trioxide intravenous infusion combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with pulmonary metastasis: long-term outcome analysis. J Gastroenterol Hepatol 32(2):295–300. https://doi.org/10.1111/jgh.13529
Hu WC, Teo WH, Huang TF, Lee TC, Lo JF (2020a) Combinatorial low dose arsenic trioxide and cisplatin exacerbates autophagy via AMPK/STAT3 signaling on targeting head and neck cancer initiating cells. Front Oncol 10:13. https://doi.org/10.3389/fonc.2020.00463
Hu XL, Cai JY, Zhu JY, Lang WJ, Zhong JH, Zhong H, Chen FY (2020b) Arsenic trioxide potentiates Gilteritinib-induced apoptosis in FLT3-ITD positive leukemic cells via IRE1a-JNK-mediated endoplasmic reticulum stress. Cancer Cell Int 20(1):14. https://doi.org/10.1186/s12935-020-01341-5
Huang SY, Chang CS, Tang JL, Tien HF, Kuo TL, Huang SF, Yao YT, Chou WC, Chung CY, Wang CH, Shen MC, Chen YC (1998) Acute and chronic arsenic poisoning associated with treatment of acute promyelocytic leukaemia. Br J Haematol 103(4):1092–1095. https://doi.org/10.1046/j.1365-2141.1998.01079.x
Huang X, Xiao Y, Jing D, Huang Y, Yang S, Huang Z, Yang G, Duan Y, He M, Su J, Chen M, Chen X, Shen M (2023) Arsenic exposure and pruritus: evidence from observational, interventional, and mendelian randomization studies. Allergy 78(6):1585–1594. https://doi.org/10.1111/all.15758
Hussein MA, Saleh M, Ravandi F, Mason J, Rifkin RM, Ellison R (2004) Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma. Br J Haematol 125(4):470–476. https://doi.org/10.1111/j.1365-2141.2004.04941.x
Iyer SG, Elias L, Stanchina M, Watts J (2022) The treatment of acute promyelocytic leukemia in 2023: paradigm, advances, and future directions. Front Oncol 12:1062524. https://doi.org/10.3389/fonc.2022.1062524
Jambrovics K, Poliska S, Scholtz B, Uray IP, Balajthy Z (2023) ATO increases ROS production and apoptosis of cells by enhancing calpain-mediated degradation of the cancer survival protein TG2. Int J Mol Sci 24(13):10938. https://doi.org/10.3390/ijms241310938
Jamil M, Mohammadi-Bardbori A, Safa O, Nikpoor AR, Bakhtari A, Mokhtarinejad M, Zadeh SN, Shadboorestan A, Omidi M (2023) Arsenic trioxide-induced cytotoxicity in A549 cells: the role of necroptosis. Drug Res (Stuttg). https://doi.org/10.1055/a-2076-3246
Jeanne M, Lallemand-Breitenbach V, Ferhi O, Koken M, Le Bras M, Duffort S, Peres L, Berthier C, Soilihi H, Raught B, de The H (2010) PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3. Cancer Cell 18(1):88–98. https://doi.org/10.1016/j.ccr.2010.06.003
Jiang C, Sun M, Li S, Tan J, Wang M, He Y (2021) Long non-coding RNA DICER1-AS1-low expression in arsenic-treated A549 cells inhibits cell proliferation by regulating the cell cycle pathway. Environ Toxicol Pharmacol 84:3617. https://doi.org/10.1016/j.etap.2021.103617
Jiang F, Li Y, Si L, Zhang Z, Li Z (2019) Interaction of EZH2 and P65 is involved in the arsenic trioxide-induced anti-angiogenesis in human triple-negative breast cancer cells. Cell Biol Toxicol 35(4):361–371. https://doi.org/10.1007/s10565-018-09458-0
Jiang L, Wang X, Raza F, Zhong H, Su J, Yuan WE, Qiu M (2023) PEG-grafted arsenic trioxide-loaded mesoporous silica nanoparticles endowed with pH-triggered delivery for liver cancer therapy. Biomater Sci 11(15):5301–5319. https://doi.org/10.1039/d3bm00555k
Jiao Y, Zhang W, Liu J, Ni W, Xu W, Jin J, Qian W (2007) Telomere attrition and chromosome instability via downregulation of TRF2 contributes to arsenic trioxide-induced apoptosis of human T-Cell leukemia cell line molt-4 cells. Cancer Biol Ther 6(8):1186–1192
Jin M, Wu L, Chen S, Cai R, Dai Y, Yang H, Tang L, Li YJ, Cdd (2020) Arsenic trioxide enhances the chemotherapeutic efficiency of cisplatin in cholangiocarcinoma cells via inhibiting the 14–3–3ε-mediated survival mechanism. Cell Death Discov 6:92. https://doi.org/10.1038/s41420-020-00330-x
Karunakaran P, Yanamandra U, Nampoothiri RV, Khadwal A, Prakash G, Lad D, Sinha A, Naseem S, Varma N, Varma S, Malhotra P (2019) Early detection of differentiation syndrome by chest ultrasound in acute promyelocytic leukaemia. Br J Haematol 184(4):672–673. https://doi.org/10.1111/bjh.15153
Kathirgamanathan K, Angaran P, Lazo-Langner A, Gula LJ (2013) Cardiac conduction block at multiple levels caused by arsenic trioxide therapy. Can J Cardiol 29(1):130. https://doi.org/10.1016/j.cjca.2012.04.004
Kchour G, Tarhini M, Kooshyar MM, El Hajj H, Wattel E, Mahmoudi M, Hatoum H, Rahimi H, Maleki M, Rafatpanah H, Rezaee SA, Yazdi MT, Shirdel A, de The H, Hermine O, Farid R, Bazarbachi A (2009) Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL). Blood 113(26):6528–6532. https://doi.org/10.1182/blood-2009-03-211821
Kepp O, Pan H, Liu P, Kroemer G (2023) Arsenic trioxide as an inducer of immunogenic cell death. Oncoimmunology 12(1):2174723. https://doi.org/10.1080/2162402X.2023.2174723
Khosravani F, Mir H, Mirzaei A, Kobarfard F, Bardania H, Hosseini E (2023) Arsenic trioxide and Erlotinib loaded in RGD-modified nanoliposomes for targeted combination delivery to PC3 and PANC-1 cell lines. Biotechnol Appl Biochem 70(2):811–823. https://doi.org/10.1002/bab.2401
Kindler HL, Aklilu M, Nattam S, Vokes EE (2008) Arsenic trioxide in patients with adenocarcinoma of the pancreas refractory to gemcitabine: a phase II trial of the University of Chicago Phase II Consortium. Am J Clin Oncol 31(6):553–556. https://doi.org/10.1097/COC.0b013e318178e4cd
Kitamura K, Minami Y, Yamamoto K, Akao Y, Kiyoi H, Saito H, Naoe T (2000) Involvement of CD95-independent caspase 8 activation in arsenic trioxide-induced apoptosis. Leukemia 14(10):1743–1750
Kühn M, Sammartin K, Nabergoj M, Vianello F, Mjoh, diseases i (2016) Severe acute axonal neuropathy following treatment with arsenic trioxide for acute promyelocytic leukemia: a case report. Mediterr J Hematol Infect Dis 8(1):e2016023. https://doi.org/10.4084/MJHID.2016.023
Kulkarni U, Mathews V (2021) Evolving chemotherapy free regimens for acute promyelocytic leukemia. Front Oncol 11:621566. https://doi.org/10.3389/fonc.2021.621566
Kumazaki M, Ando H, Kakei M, Ushijima K, Taniguchi Y, Yoshida M, Yamato S, Washino S, Koshimizu T-a, Fujimura A (2013) alpha-Lipoic acid protects against arsenic trioxide-induced acute QT prolongation in anesthetized guinea pigs. Eur J Pharmacol 705(1–3):1–10. https://doi.org/10.1016/j.ejphar.2013.02.027
Kuroki M, Ariumi Y, Ikeda M, Dansako H, Wakita T, Kato N (2009) Arsenic trioxide inhibits hepatitis C virus RNA replication through modulation of the glutathione redox system and oxidative stress. J Virol 83(5):2338–2348. https://doi.org/10.1128/JVI.01840-08
Kuszczak B, Wrobel T, Wicherska-Pawlowska K, Rybka J (2023) The role of BCL-2 and PD-1/PD-L1 pathway in pathogenesis of myelodysplastic syndromes. Int J Mol Sci 24(5):10. https://doi.org/10.3390/ijms24054708
Kutny MA, Alonzo TA, Abla O, Rajpurkar M, Gerbing RB, Wang Y-C, Hirsch BA, Raimondi S, Kahwash S, Hardy KK, Hardy S, Meshinchi S, Gamis AS, Kolb EA, Feusner JH, Gregory J (2022) Assessment of arsenic trioxide and all-trans retinoic acid for the treatment of pediatric acute promyelocytic leukemia: a report from the Children’s Oncology Group AAML1331 Trial. JAMA Oncol 8(1):79–87. https://doi.org/10.1001/jamaoncol.2021.5206
Lakshmaiah KC, Chaudhuri T, Babu GK, Lokanatha D, Jacob LA, Suresh Babu MC, Rudresha AH, Lokesh KN, Rajeev LK (2017) Safety and antitumor activity of arsenic trioxide plus infusional 5-fluorouracil, leucovorin, and irinotecan as second-line chemotherapy for refractory metastatic colorectal cancer: a pilot study from South India. Indian J Cancer 54(4):631–633. https://doi.org/10.4103/ijc.IJC_374_17
Lallemand-Breitenbach V, Jeanne M, Benhenda S, Nasr R, Lei M, Peres L, Zhou J, Zhu J, Raught B, de The H (2008) Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway. Nat Cell Biol 10(5):547–555. https://doi.org/10.1038/ncb1717
Lam HK, Li K, Chik KW, Yang M, Liu VC, Li CK, Fok TF, Ng PC, Shing MM, Chuen CK, Yuen PM (2005) Arsenic trioxide mediates intrinsic and extrinsic pathways of apoptosis and cell cycle arrest in acute megakaryocytic leukemia. Int J Oncol 27(2):537–545
Lauricella C, Greco R, Mancini V, Motta V, Ciraolo A, De Canal G, De Paoli E, Paglino G, Guido V, Bonoldi E, Veronese S, Soriani S (2023) Acute promyelocytic leukemia with del(6)(p22) and Atypical bcr2 PML::RARA fusion transcript: a case report. Acta Haematol 146(1):58–64. https://doi.org/10.1159/000527316
Lazo G, Kantarjian H, Estey E, Thomas D, O’Brien S, Cortes J (2003) Use of arsenic trioxide (As2O3) in the treatment of patients with acute promyelocytic leukemia: the M.D. Anderson. Exp Cancer 97(9):2218–2224. https://doi.org/10.1002/cncr.11314
Li C, Zhang J, Wang W, Wang H, Zhang Y, Zhang Z (2019) Arsenic trioxide improves Treg and Th17 balance by modulating STAT3 in treatment-naïve rheumatoid arthritis patients. Int Immunopharmacol 73:539–551. https://doi.org/10.1016/j.intimp.2019.05.001
Li HC, Wang CX, Huang C, Wang LF, Mu XY, Jiang SJ, Lei ML (2003) Effect and mechanism of arsenic trioxide on chemosensitivity of human lung adenocarcinoma cells. Chin J Tuberc Respir Dis 26(11):689–692
Li J-X, Shen Y-Q, Cai B-Z, Zhao J, Bai X, Lu Y-J, Li X-Q (2010) Arsenic trioxide induces the apoptosis in vascular smooth muscle cells via increasing intracellular calcium and ROS formation. Mol Biol Rep 37(3):1569–1576. https://doi.org/10.1007/s11033-009-9561-z
Li J, Tang G, Qin W, Yang R, Ma R, Ma B, Wei J, Lv H, Jiang Y (2018a) Toxic effects of arsenic trioxide on Echinococcus granulosus protoscoleces through ROS production, and Ca2+-ER stress-dependent apoptosis. Acta Biochim Biophys Sin (Shanghai) 50(6):579–585. https://doi.org/10.1093/abbs/gmy041
Li T, Ma R, Zhang Y, Mo H, Yang X, Hu S, Wang L, Novakovic VA, Chen H, Kou J, Bi Y, Yu B, Fang S, Wang J, Zhou J, Shi J (2018b) Arsenic trioxide promoting ETosis in acute promyelocytic leukemia through mTOR-regulated autophagy. Cell Death Dis 9(2):75. https://doi.org/10.1038/s41419-017-0018-3
Li X, Sun D, Zhao T, Zhang Z (2020) Long non-coding RNA ROR confers arsenic trioxide resistance to HepG2 cells by inhibiting p53 expression. Eur J Pharmacol. 872:172982. https://doi.org/10.1016/j.ejphar.2020.172982
Li Y, Sun X, Wang L, Zhou Z, Kang YJ (2002) Myocardial toxicity of arsenic trioxide in a mouse model. Cardiovasc Toxicol 2(1):63–73. https://doi.org/10.1385/CT:2:1:63
Li YM, Broome JD (1999) Arsenic targets tubulins to induce apoptosis in myeloid leukemia cells. Can Res 59(4):776–780
Liang Y, Zheng B, Li J, Shi J, Chu L, Han X, Chu X, Zhang X, Zhang JJB (2020) Crocin ameliorates arsenic trioxide-induced cardiotoxicity via Keap1-Nrf2/HO-1 pathway: reducing oxidative stress, inflammation, and apoptosis. Biomed Pharmacother 131:110713. https://doi.org/10.1016/j.biopha.2020.110713
Lin CC, Hsu C, Hsu CH, Hsu WL, Cheng AL, Yang CH (2007) Arsenic trioxide in patients with hepatocellular carcinoma: a phase II trial. Invest New Drugs 25(1):77–84. https://doi.org/10.1007/s10637-006-9004-9
Liu J, Li X, Chen J, Zhang X, Guo J, Gu J, Mei C, Xiao Y, Peng C, Liu J, Hu X, Zhang K, Li D, Zhou B (2023) Arsenic-loaded biomimetic iron oxide nanoparticles for enhanced ferroptosis-inducing therapy of hepatocellular carcinoma. ACS Appl Mater Interfaces 15(5):6260–6273. https://doi.org/10.1021/acsami.2c14962
Liu J, Zheng B, Aposhian HV, Zhou Y, Chen M-L, Zhang A, Waalkes MP (2002a) Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China. Environ Health Perspect 110(2):119–122
Liu L, Trimarchi JR, Smith PJ, Keefe DL (2002b) Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell 1(1):40–46. https://doi.org/10.1046/j.1474-9728.2002.00004.x
Liu Q, Hilsenbeck S, Gazitt Y (2003) Arsenic trioxide-induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL. Blood 101(10):4078–4087. https://doi.org/10.1182/blood-2002-10-3231
Lu PH, Tseng JC, Chen CK, Chen CH (2017) Survival without peripheral neuropathy after massive acute arsenic poisoning: Treated by 2,3-dimercaptopropane-1-sulphonate. J Clin Pharm Ther 42(4):506–508. https://doi.org/10.1111/jcpt.12538
Maimaitiyiming Y, Wang QQ, Hsu CH, Naranmandura H (2020) Arsenic induced epigenetic changes and relevance to treatment of acute promyelocytic leukemia and beyond. Toxicol Appl Pharmacol 406:115212. https://doi.org/10.1016/j.taap.2020.115212
Mao J, Shi X, Hua L, Yang M, Shen Y, Ruan Z, Li B, Xi X (2023) Arsenic inhibits proliferation and induces autophagy of tumor cells in pleural effusion of patients with non-small cell lung cancer expressing EGFR with or without mutations via PI3K/AKT/mTOR pathway. Biomedicines 11(6):1721. https://doi.org/10.3390/biomedicines11061721
Marcais A, Cook L, Witkover A, Asnafi V, Avettand-Fenoel V, Delarue R, Cheminant M, Sibon D, Frenzel L, de The H, Bangham CRM, Bazarbachi A, Hermine O, Suarez F (2020) Arsenic trioxide (As(2)O(3)) as a maintenance therapy for adult T cell leukemia/lymphoma. Retrovirology 17(1):5. https://doi.org/10.1186/s12977-020-0513-y
Mathas S, Lietz A, Janz M, Hinz M, Jundt F, Scheidereit C, Bommert K, Dorken B (2003) Inhibition of NF-kappaB essentially contributes to arsenic-induced apoptosis. Blood 102(3):1028–1034. https://doi.org/10.1182/blood-2002-04-1154
Miller WH Jr, Schipper HM, Lee JS, Singer J, Waxman S (2002) Mechanisms of action of arsenic trioxide. Can Res 62(14):3893–3903
Moodad S, El Hajj R, Hleihel R, Hajjar L, Tawil N, Karam M, Hamie M, Abou Merhi R, El Sabban M, El Hajj H (2020) Lenalidomide in combination with arsenic trioxide: an effective therapy for primary effusion lymphoma. Cancers 12(9):19. https://doi.org/10.3390/cancers12092483
Munshi NC, Tricot G, Desikan R, Badros A, Zangari M, Toor A, Morris C, Anaissie E, Barlogie B (2002) Clinical activity of arsenic trioxide for the treatment of multiple myeloma. Leukemia 16(9):1835–1837. https://doi.org/10.1038/sj.leu.2402599
Nassar M, Dargham A, Hiraishi N, Tamura Y, Tagami J (2020) In vitro mitigation of arsenic-induced toxicity by reduced glutathione in rat pulp cells. Eur Endod J 5(3):277–281. https://doi.org/10.14744/eej.2020.26878
Ng Liet Hing M, Ryland GL, Nguyen T, Tiong IS, Dun K, Ninkovic S, Nedumannil R, Westerman DA, Blombery PA, Chan KL, Bajel A (2023) Variant acute promyelocytic leukaemia with novel NAB2::RARA fusion shows clinical all-trans retinoic acid and arsenic trioxide sensitivity. Br J Haematol 202(4):893–896. https://doi.org/10.1111/bjh.18907
Nithyananthan S, Thirunavukkarasu C (2019) Chemotherapeutic doses of arsenic trioxide delays hepatic regeneration by oxidative stress and hepatocyte apoptosis in partial hepatectomy rat. Toxicol Appl Pharmacol 382:114760. https://doi.org/10.1016/j.taap.2019.114760
Ommati MM, Heidari R, Manthari RK, Tikka Chiranjeevi S, Niu R, Sun Z, Sabouri S, Zamiri MJ, Zaker L, Yuan J, Wang J, Zhang J, Wang J (2019) Paternal exposure to arsenic resulted in oxidative stress, autophagy, and mitochondrial impairments in the HPG axis of pubertal male offspring. Chemosphere 236:124325. https://doi.org/10.1016/j.chemosphere.2019.07.056
Ommati MM, Shi X, Li H, Zamiri MJ, Farshad O, Jamshidzadeh A, Heidari R, Ghaffari H, Zaker L, Sabouri S, Chen Y (2020) The mechanisms of arsenic-induced ovotoxicity, ultrastructural alterations, and autophagic related paths: an enduring developmental study in folliculogenesis of mice. Ecotoxicol Environ Saf 204:110973. https://doi.org/10.1016/j.ecoenv.2020.110973
Owonikoko TK, Zhang G, Kim HS, Stinson RM, Bechara R, Zhang C, Chen Z, Saba NF, Pakkala S, Pillai R, Deng X, Sun SY, Rossi MR, Sica GL, Ramalingam SS, Khuri FR (2016) Patient-derived xenografts faithfully replicated clinical outcome in a phase II co-clinical trial of arsenic trioxide in relapsed small cell lung cancer. J Transl Med 14(1):111. https://doi.org/10.1186/s12967-016-0861-5
Pei P, Yao X, Jiang L, Qiu T, Wang N, Yang L, Gao N, Wang Z, Yang G, Liu X, Liu S, Jia X, Tao Y, Wei S, Sun X (2019) Inorganic arsenic induces pyroptosis and pancreatic beta cells dysfunction through stimulating the IRE1alpha/TNF-alpha pathway and protective effect of taurine. Food Chem Toxicol 125:392–402. https://doi.org/10.1016/j.fct.2019.01.015
Qian W, Wang L, Li P, Hu Y, Wang Q, Yi K, Wu M, Xu Y, Song J, Chen P, Zhang H, Ma J, Xie Y (2020) Efficiency and tolerability of induction and consolidation therapy with arsenic trioxide/bortezomib/ascorbic acid/dexamethasone (ABCD) regimen compared to bortezomib/dexamethasone (BD) regimen in newly diagnosed myeloma patients. Cancer Manag Res 12:431–441. https://doi.org/10.2147/CMAR.S212455
Qiu T, Pei P, Yao X, Jiang L, Wei S, Wang Z, Bai J, Yang G, Gao N, Yang L, Qi S, Yan R, Liu X, Sun X (2018) Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway. Cell Death Dis 9(10):946. https://doi.org/10.1038/s41419-018-1004-0
Raffoul F, Campla C, Nanjundan M (2010) SnoN/SkiL, a TGFbeta signaling mediator: a participant in autophagy induced by arsenic trioxide. Autophagy 6(7):955–957. https://doi.org/10.4161/auto.6.7.13041
Ranieri R, Pianigiani G, Sciabolacci S, Perriello VM, Marra A, Cardinali V, Pierangeli S, Milano F, Gionfriddo I, Brunetti L, Martelli MP, Falini B (2022) Current status and future perspectives in targeted therapy of NPM1-mutated AML. Leukemia 36(10):2351–2367. https://doi.org/10.1038/s41375-022-01666-2
Roboz GJ, Dias S, Lam G, Lane WJ, Soignet SL, Warrell RP Jr, Rafii S (2000) Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood 96(4):1525–1530
Roboz GJ, Ritchie EK, Carlin RF, Samuel M, Gale L, Provenzano-Gober JL, Curcio TJ, Feldman EJ, Kligfield PD (2014) Prevalence, management, and clinical consequences of QT interval prolongation during treatment with arsenic trioxide. J Clin Oncol 32(33):3723–3728. https://doi.org/10.1200/JCO.2013.51.2913
Roboz GJ, Ritchie EK, Curcio T, Provenzano J, Carlin R, Samuel M, Wittenberg B, Mazumdar M, Christos PJ, Mathew S, Allen-Bard S, Feldman EJ (2008) Arsenic trioxide and low-dose cytarabine in older patients with untreated acute myeloid leukemia, excluding acute promyelocytic leukemia. Cancer 113(9):2504–2511. https://doi.org/10.1002/cncr.23855
Roboz GJ, Ritchie EK, Curcio T, Samuel M, Provenzano J, Segovia J, Christos PJ, Mathew S, Allen-Bard S, Feldman EJ (2011) Arsenic trioxide and low-dose cytarabine for patients with intermediate-2 and high-risk myelodysplastic syndrome. Leuk Res 35(4):522–525. https://doi.org/10.1016/j.leukres.2010.09.010
Rojewski MT, Baldus C, Knauf W, Thiel E, Schrezenmeier H (2002) Dual effects of arsenic trioxide (As2O3) on non-acute promyelocytic leukemia myeloid cell lines: induction of apoptosis and inhibition of proliferation. Br J Haematol. https://doi.org/10.0000/000368496328740
Rosati G, Camerlo S, Dalmazzo M, Padrini M, Busana TT, De Gobbi M, Fornari A, Morotti A (2023) Acute promyelocytic leukemia and brugada syndrome: a report on the safety of arsenic trioxide/all-trans-retinoic acid therapy. Hematol Rep 15(3):440–447. https://doi.org/10.3390/hematolrep15030045
Rousselot P, Larghero J, Arnulf B, Poupon J, Royer B, Tibi A, Madelaine-Chambrin I, Cimerman P, Chevret S, Hermine O, Dombret H, Claude Brouet J, Paul Fermand J (2004) A clinical and pharmacological study of arsenic trioxide in advanced multiple myeloma patients. Leukemia 18(9):1518–1521. https://doi.org/10.1038/sj.leu.2403424
Sadaf N, Kumar N, Ali M, Ali V, Bimal S, Haque R (2018a) Arsenic trioxide induces apoptosis and inhibits the growth of human liver cancer cells. Life Sci 205:9–17. https://doi.org/10.1016/j.lfs.2018.05.006
Sadaf N, Kumar N, Ali M, Ali V, Bimal S, Haque R (2018) Arsenic trioxide induces apoptosis and inhibits the growth of human liver cancer cells. Life Sci 205:9–17. https://doi.org/10.1016/j.lfs.2018.05.006
Schiller GJ, Slack J, Hainsworth JD, Mason J, Saleh M, Rizzieri D, Douer D, List AF (2006) Phase II multicenter study of arsenic trioxide in patients with myelodysplastic syndromes. J Clin Oncol 24:2456–2464. https://doi.org/10.1200/jco.2005.03.7903
Shan H, Zhang Y, Cai B, Chen X, Fan Y, Yang L, Chen X, Liang H, Zhang Y, Song X, Xu C, Lu Y, Yang B, Du Z (2013) Upregulation of microRNA-1 and microRNA-133 contributes to arsenic-induced cardiac electrical remodeling. Int J Cardiol 167(6):2798–2805. https://doi.org/10.1016/j.ijcard.2012.07.009
Shen X, Zhi F, Shi C, Xu J, Chao Y, Xu J, Jiang Y, Bai Y, Yang B (2023a) The involvement and therapeutic potential of lncRNA Kcnq1ot1/miR-34a-5p/Sirt1 pathway in arsenic trioxide-induced cardiotoxicity. J Transl Med 21(1):52. https://doi.org/10.1186/s12967-023-03895-0
Shen Y, Zhang R, Li X (2023b) Identification of eIF6 as a prognostic factor that drives tumor progression and predicts arsenic trioxide efficacy in lung adenocarcinoma. Mol Biol Rep 50(2):1167–1180. https://doi.org/10.1007/s11033-022-07917-w
Shi Y, Cao T, Huang H, Lian C, Yang Y, Wang Z, Ma J, Xia J (2017) Arsenic trioxide inhibits cell growth and motility via up-regulation of let-7a in breast cancer cells. Cell Cycle 16(24):2396–2403. https://doi.org/10.1080/15384101.2017.1387699
Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E, Stone RM, Kalaycio M, Scheinberg DA, Steinherz P, Sievers EL, Coutre S, Dahlberg S, Ellison R, Warrell RP Jr (2001) United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol 19(18):3852–3860. https://doi.org/10.1200/JCO.2001.19.18.3852
Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ, Corso D, DeBlasio A, Gabrilove J, Scheinberg DA, Pandolfi PP, Warrell RP Jr (1998) Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 339(19):1341–1348. https://doi.org/10.1056/NEJM199811053391901
Stahl M, Tallman MS (2019) Differentiation syndrome in acute promyelocytic leukaemia. Br J Haematol 187(2):157–162. https://doi.org/10.1111/bjh.16151
Sun HL, Chu WF, Dong DL, Liu Y, Bai YL, Wang XH, Zhou J, Yang BF (2006) Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization in Guinea pig. Basic Clin Pharmacol Toxicol 98(4):381–388. https://doi.org/10.1111/j.1742-7843.2006.pto_319.x
Sun RC, Board PG, Blackburn AC (2011) Targeting metabolism with arsenic trioxide and dichloroacetate in breast cancer cells. Mol Cancer 10:15. https://doi.org/10.1186/1476-4598-10-142
Sun Y, Wang C, Wang L, Dai Z, Yang K (2018a) Arsenic trioxide induces apoptosis and the formation of reactive oxygen species in rat glioma cells. Cell Mol Biol Lett 23:13. https://doi.org/10.1186/s11658-018-0074-4
Sun Y, Wang C, Wang L, Dai Z, Yang K (2018) Arsenic trioxide induces apoptosis and the formation of reactive oxygen species in rat glioma cells. Cell Mol Biol Lett 23(1):1–10. https://doi.org/10.1186/s11658-018-0074-4
Sun Y, Wang L, Que Y, Zhu H, Yang X, Li D (2020) Ventricular repolarization dynamics in arsenic trioxide treatment of acute promyelocytic leukemia. Int J Cardiol 306:163–167. https://doi.org/10.1016/j.ijcard.2019.11.099
Sun Z, Cao Y, Xing Y, Wu M, Shao X, Huang Q, Bai L, Wang L, Zhao Y, Wu Y (2021) Antiangiogenic effect of arsenic trioxide in HUVECs by FoxO3a-regulated autophagy. J Biochem Mol Toxicol 35(5):e22728. https://doi.org/10.1002/jbt.22728
Suzuki T, Ishibashi K, Yumoto A, Nishio K, Ogasawara Y (2015) Utilization of arsenic trioxide as a treatment of cisplatin-resistant non-small cell lung cancer PC-9/CDDP and PC-14/CDDP cells. Oncol Lett 10(2):805–809. https://doi.org/10.3892/ol.2015.3352
Wu S, Rao G, Wang R, Pang Q, Zhang X, Huang R, Li T, Tang Z, Hu L (2021) The neuroprotective effect of curcumin against ATO triggered neurotoxicity through Nrf2 and NF-κB signaling pathway in the brain of ducks. Ecotoxicol Environ Saf. 228:2965. https://doi.org/10.1016/j.ecoenv.2021.112965
Tang S, Shen Y, Wei X, Shen Z, Lu W, Xu J (2022) Olaparib synergizes with arsenic trioxide by promoting apoptosis and ferroptosis in platinum-resistant ovarian cancer. Cell Death Dis 13(9):826. https://doi.org/10.1038/s41419-022-05257-y
Tian W, Wang Z, Tang NN, Li JT, Liu Y, Chu WF, Yang BF (2020) Ascorbic acid sensitizes colorectal carcinoma to the cytotoxicity of arsenic trioxide via promoting reactive oxygen species-dependent apoptosis and pyroptosis. Front Pharmacol 11:123. https://doi.org/10.3389/fphar.2020.00123
Tian Z, Tan Y, Lin X, Su M, Pan L, Lin L, Ou G, Chen Y (2023) Arsenic trioxide sensitizes pancreatic cancer cells to gemcitabine through downregulation of the TIMP1/PI3K/AKT/mTOR axis. Transl Res 255:66–76. https://doi.org/10.1016/j.trsl.2022.11.007
Tsai SM, Wang TN, Ko YC (1999) Mortality for certain diseases in areas with high levels of arsenic in drinking water. Arch Environ Health 54(3):186–193
Valberg PA, Beck BD, Bowers TS, Keating JL, Bergstrom PD, Boardman PD (1997) Issues in setting health-based cleanup levels for arsenic in soil. Regul Toxicol Pharmacol 26(2):219–229. https://doi.org/10.1006/rtph.1997.1148
Varghese MV, Abhilash M, Paul MV, Alex M, Nair RH (2017) Omega-3 fatty acid protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo. Cardiovasc Toxicol 17(2):109–119. https://doi.org/10.1007/s12012-016-9361-3
Vey N, Bosly A, Guerci A, Feremans W, Dombret H, Dreyfus F, Bowen D, Burnett A, Dennis M, Ribrag V, Casadevall N, Legros L, Fenaux P (2006) Arsenic trioxide in patients with myelodysplastic syndromes: a phase II multicenter study. J Clin Oncol 24(16):2465–2471. https://doi.org/10.1200/jco.2005.03.9503
Vineetha VP, Girija S, Soumya RS, Raghu KG (2014) Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity. Food Funct 5(3):502–511. https://doi.org/10.1039/c3fo60470e
Wang H, Liu Y, Wang X, Liu D, Sun Z, Wang C, Jin G, Zhang B, Yu S (2015) Randomized clinical control study of locoregional therapy combined with arsenic trioxide for the treatment of hepatocellular carcinoma. Cancer 121(17):2917–2925. https://doi.org/10.1002/cncr.29456
Wang HY, Zhang B, Zhou JN, Wang DX, Xu YC, Zeng Q, Jia YL, Xi JF, Nan X, He LJ, Yue W (2019) Arsenic trioxide inhibits liver cancer stem cells and metastasis by targeting SRF/MCM7 complex. Cell Death Dis 10(6):453. https://doi.org/10.1038/s41419-019-1676-0
Wang HY, Gong S, Li GH, Yao YZ, Zheng YS, Lu XH, Wei SH, Qin WW, Liu HB, Wang MC, Xi JY, Chen LM, Zhang M, Zhang XX, Zhang HY, Zhang CS, Wald DN, Zhu HH, Liu L, He PC (2022a) An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial). Blood Cancer J 12(11):158. https://doi.org/10.1038/s41408-022-00753-y
Wang J, Liu YM, Hu J, Chen C (2023a) Potential of natural products in combination with arsenic trioxide: investigating cardioprotective effects and mechanisms. Biomed Pharmacother 162:114464. https://doi.org/10.1016/j.biopha.2023.114464
Wang J, Zhan L, Cai Z, Liu X, Wang J, Zhong H, Huang X, Lai Q, Tan Q, Xiu Y, Yang D, Min X (2020a) Arsenic trioxide induces gasdermin E mediated pyroptosis in astroglioma cells. Transl Cancer Res 9(3):1926–1930. https://doi.org/10.21037/tcr.2020.02.17
Wang QQ, Hua HY, Naranmandura H, Zhu HH (2020b) Balance between the toxicity and anticancer activity of arsenic trioxide in treatment of acute promyelocytic leukemia. Toxicol Appl Pharmacol 409:115299. https://doi.org/10.1016/j.taap.2020.115299
Wang QQ, Jiang Y, Naranmandura H (2020c) Therapeutic strategy of arsenic trioxide in the fight against cancers and other diseases. Metallomics 12(3):326–336. https://doi.org/10.1039/c9mt00308h
Wang R, Zhang J, Wang S, Wang M, Ye T, Du Y, Xie X, Ye J, Sun G, Sun X (2019) The cardiotoxicity induced by arsenic trioxide is alleviated by salvianolic acid A via maintaining calcium homeostasis and inhibiting endoplasmic reticulum stress. Molecules. https://doi.org/10.3390/molecules24030543
Wang W, Adachi M, Zhang R, Zhou J, Zhu DL (2009) A novel combination therapy with arsenic trioxide and parthenolide against pancreatic cancer cells. Pancreas 38(4):E114–E123. https://doi.org/10.1097/MPA.0b013e3181a0b6f2
Wang XB, Yuan LH, Yan LP, Ye YB, Lu B, Xu X (2022b) UNC13B promote arsenic trioxide resistance in chronic lymphoid leukemia through mitochondria quality control. Front Oncol 12:920999. https://doi.org/10.3389/fonc.2022.920999
Wang Y, Jiang F, Jiao K, Ju L, Liu Q, Li Y, Miao L, Li Z (2020) De-methylation of miR-148a by arsenic trioxide enhances sensitivity to chemotherapy via inhibiting the NF-κB pathway and CSC like properties. Exp Cell Res. 386(2):111739. https://doi.org/10.1016/j.yexcr.2019.111739
Wang Y, Zhang Y, Yang L, Cai B, Li J, Zhou Y, Yin L, Yang L, Yang BF, Lu YJ (2011) Arsenic trioxide induces the apoptosis of human breast cancer MCF-7 cells through activation of caspase-3 and inhibition of HERG channels. Exp Ther Med 2(3):481–486. https://doi.org/10.3892/etm.2011.224
Wang YS, Yin JZ, Shi XQ, Zhao XW, Li B, Yang MH (2023b) MDM2-mediated inhibitory effect of arsenic trioxide on small cell lung cancer cell line by degrading mutant p53. Anticancer Agents Med Chem. https://doi.org/10.2174/1871520623666230530095435
Wang YT, Zhang W, Chen L, Chen W, Xu SF, Tang LY, Yang Y, Li QP, Jiang Q, Miao L (2021) The ATO/miRNA-885-5p/MTPN axis induces reversal of drug-resistance in cholangiocarcinoma. Cell Oncol 44(4):907–916. https://doi.org/10.1007/s13402-021-00610-3
Wei W, Zhou F, Zhang Y, Guo L, Shi H, Hou J (2012) A combination of thalidomide and arsenic trioxide is effective and well tolerated in patients with myelodysplastic syndromes. Leuk Res 36(6):715–719. https://doi.org/10.1016/j.leukres.2011.12.023
Wen J, Feng Y, Huang W, Chen H, Liao B, Rice L, Preti HA, Kamble RT, Zu Y, Ballon DJ, Chang CC (2010) Enhanced antimyeloma cytotoxicity by the combination of arsenic trioxide and bortezomib is further potentiated by p38 MAPK inhibition. Leuk Res 34(1):85–92. https://doi.org/10.1016/j.leukres.2009.05.024
Wetzler M, Andrews C, Ford LA, Tighe S, Barcos M, Sait SN, Block AW, Nowak NJ, Baer MR, Wang ES, Baumann H (2011) Phase 1 study of arsenic trioxide, high-dose cytarabine, and idarubicin to down-regulate constitutive signal transducer and activator of transcription 3 activity in patients aged <60 years with acute myeloid leukemia. Cancer 117(21):4861–4868. https://doi.org/10.1002/cncr.26097
Wilcken R, Wang GZ, Boeckler FM, Fersht AR (2012) Kinetic mechanism of p53 oncogenic mutant aggregation and its inhibition. Proc Natl Acad Sci USA 109(34):13584–13589. https://doi.org/10.1073/pnas.1211550109
Woo SH, Park IC, Park MJ, An S, Lee HC, Jin HO, Park SA, Cho H, Lee SJ, Gwak HS, Hong YJ, Hong SI, Rhee CH (2004) Arsenic trioxide sensitizes CD95/Fas-induced apoptosis through ROS-mediated upregulation of CD95/Fas by NF-kappaB activation. Int J Cancer 112(4):596–606. https://doi.org/10.1002/ijc.20433
Wu B, Tan M, Cai W, Wang B, He P, Zhang X (2018) Arsenic trioxide induces autophagic cell death in osteosarcoma cells via the ROS-TFEB signaling pathway. Biochem Biophys Res Commun 496(1):167–175. https://doi.org/10.1016/j.bbrc.2018.01.018
Wu M, Pang C, Lu S, Hostetter TH, Hai X (2023) Type 2 diabetes affects arsenic metabolism via transporters in arsenic trioxide treated acute promyelocytic leukemia patients. Environ Toxicol Pharmacol 100:104142. https://doi.org/10.1016/j.etap.2023.104142
Wu SF, Yu WL, Jiang XX, Huang RM, Zhang XY, Lan J, Zhong GL, Wan F, Tang ZX, Hu LM (2021) Protective effects of curcumin on ATO-induced nephrotoxicity in ducks in relation to suppressed autophagy, apoptosis and dyslipidemia by regulating oxidative stress. Ecotox Environ Safe 219:11. https://doi.org/10.1016/j.ecoenv.2021.112350
Wu X, Han Z, Schur RM, Lu ZR (2016) Targeted mesoporous silica nanoparticles delivering arsenic trioxide with environment sensitive drug release for effective treatment of triple negative breast cancer. ACS Biomater Sci Eng 2(4):501–507. https://doi.org/10.1021/acsbiomaterials.5b00398
Xu H, Li C, Wei Y, Zheng H, Zheng H, Wang B, Piao JG, Li F (2021) Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy. Biochem Biophys Res Commun 551:14–20. https://doi.org/10.1016/j.bbrc.2021.02.138
Yan M, Feng L, Shi Y, Wang J, Liu Y, Li F, Li B (2017) Mechanism of As2O3-induced action potential prolongation and using hiPS-CMs to evaluate the rescue efficacy of drugs with different rescue mechanism. Toxicol Sci 158(2):379–390. https://doi.org/10.1093/toxsci/kfx098
Yang GF, Li XH, Zhao Z, Wang WB (2010) Arsenic trioxide up-regulates Fas expression in human osteosarcoma cells. Chin Med J 123(13):1768–1773
Yang MH, Chang KJ, Zheng JC, Huang H, Sun GY, Zhao XW, Li B, Xiu QY (2017) Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation. Oncol Lett 14(3):3103–3109. https://doi.org/10.3892/ol.2017.6518
Yang Q, Feng F, Li P, Pan E, Wu C, He Y, Zhang F, Zhao J, Li R, Feng L, Hu F, Li L, Zou H, Cai W, Lehner T, Sun C, Chen L (2019) Arsenic trioxide impacts viral latency and delays viral rebound after termination of ART in chronically SIV-infected macaques. Adv Sci 6(13):1900319. https://doi.org/10.1002/advs.201900319
Yang Q, Feng F, Li P, Pan E, Wu C, He Y, Zhang F, Zhao J, Li R, Feng L, Hu F, Li L, Zou H, Cai W, Lehner T, Sun C, Chen L (2019b) Arsenic trioxide impacts viral latency and delays viral rebound after termination of ART in chronically SIV-infected macaques. Adv Sci (weinh) 6(13):1900319. https://doi.org/10.1002/advs.201900319
Yao H, Wu QL, Wang HM, Fan J (2005) [Effects of arsenic trioxideon the cell apoptosis and hTERT mRNA of human tongue cancer cells]. Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China J Stomatol 23(5):442–444, 448.
Ye Y, Ricard L, Siblany L, Stocker N, De Vassoigne F, Brissot E, Lamarthee B, Mekinian A, Mohty M, Gaugler B, Malard F (2020) Arsenic trioxide induces regulatory functions of plasmacytoid dendritic cells through interferon- alpha inhibition. Acta Pharm Sin B 10(6):1061–1072. https://doi.org/10.1016/j.apsb.2020.01.016
Yi J, Gong X, Yin XY, Wang L, Hou JX, Chen J, Xie B, Chen G, Wang LN, Wang XY, Wang DC, Wei HL (2022) Parthenolide and arsenic trioxide co-trigger autophagy-accompanied apoptosis in hepatocellular carcinoma cells. Front Oncol 12:988528. https://doi.org/10.3389/fonc.2022.988528
You BR, Park WH (2012) Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncol Rep 28(2):749–757. https://doi.org/10.3892/or.2012.1852
Yu M, Zhang Y, Fang M, Jehan S, Zhou W (2022) Current advances of nanomedicines delivering arsenic trioxide for enhanced tumor therapy. Pharmaceutics 14(4):743. https://doi.org/10.3390/pharmaceutics14040743
Yu S, Wu N, Zhu J, Liu Y, Han J (2020a) Pyrrolidine dithiocarbamate facilitates arsenic trioxide against pancreatic cancer via perturbing ubiquitin-proteasome pathway. Cancer Manag Res 12:13149–13159. https://doi.org/10.2147/CMAR.S278674
Yu S, Wu N, Zhu J, Liu Y, Han J (2020) Pyrrolidine dithiocarbamate facilitates arsenic trioxide against pancreatic cancer via perturbing ubiquitin-proteasome pathway. Cancer Manag Res 12:13149–13159. https://doi.org/10.2147/cmar.S278674
Zeng YJ, Liu F, Wu M, Wu XP, Zhang DL, Yuan QQ, Zhou L, Wu ZH (2023) Curcumin combined with arsenic trioxide in the treatment of acute myeloid leukemia: network pharmacology analysis and experimental validation. J Cancer Res Clin Oncol 149(1):219–230. https://doi.org/10.1007/s00432-022-04463-7
Zhai Y, Liu M, Yang T, Luo J, Wei C, Shen J, Song X, Ke H, Sun P, Guo M, Deng Y, Chen H (2022) Self-activated arsenic manganite nanohybrids for visible and synergistic thermo/immuno-arsenotherapy. J Control Release 350:761–776. https://doi.org/10.1016/j.jconrel.2022.08.054
Zhang BB, Chen XJ, Fan XD, Zhu JJ, Wei YH, Zheng HS, Zheng HY, Wang BH, Piao JG, Li FZ (2021a) Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells. Acta Pharmacol Sin 42(5):832–842. https://doi.org/10.1038/s41401-021-00648-x
Zhang JY, Sun GB, Wang M, Liao P, Du YY, Yang K, Sun XB (2016a) Arsenic trioxide triggered calcium homeostasis imbalance and induced endoplasmic reticulum stress-mediated apoptosis in adult rat ventricular myocytes. Toxicol Res (camb) 5(2):682–688. https://doi.org/10.1039/c5tx00463b
Zhang JY, Zhang B, Wang M, Wang W, Liao P, Sun GB, Sun XB (2017) Calcium homeostasis and endoplasmic reticulum stress are involved in Salvianolic acid B-offered protection against cardiac toxicity of arsenic trioxide. Oncotarget 8(57):97384–97393. https://doi.org/10.18632/oncotarget.22127
Zhang L, Zhou Y, Kong J, Zhang L, Yuan M, Xian S, Wang Y, Cheng Y, Yang X (2020a) Effect of arsenic trioxide on cervical cancer and its mechanisms. Exp Ther Med 20(6):169. https://doi.org/10.3892/etm.2020.9299
Zhang L, Zhou Y, Kong J, Zhang L, Yuan M, Xian S, Wang Y, Cheng Y, Yang XJE, Medicine t (2020) Effect of arsenic trioxide on cervical cancer and its mechanisms. Exp Ther Med 20(6):169. https://doi.org/10.3892/etm.2020.9299
Zhang L, Zou Y, Chen Y, Guo Y, Yang W, Chen X, Wang S, Liu X, Ruan M, Zhang J, Liu T, Liu F, Qi B, An W, Ren Y, Chang L, Zhu X (2018) Role of cytarabine in paediatric acute promyelocytic leukemia treated with the combination of all-trans retinoic acid and arsenic trioxide: a randomized controlled trial. BMC Cancer 18(1):374. https://doi.org/10.1186/s12885-018-4280-2
Zhang SH, Ma C, Pang HJ, Zeng FP, Cheng L, Fang BB, Ma J, Shi Y, Hong HY, Chen JY, Wang ZW, Xia J (2016b) Arsenic trioxide suppresses cell growth and migration via inhibition of miR-27a in breast cancer cells. Biochem Biophys Res Commun 469(1):55–61. https://doi.org/10.1016/j.bbrc.2015.11.071
Zhang TC, Cao EH, Li JF, Ma W, Qin JF (1999) Induction of apoptosis and inhibition of human gastric cancer MGC-803 cell growth by arsenic trioxide. Eur J Cancer 35(8):1258–1263
Zhang W, Guo C, Gao R, Ge M, Zhu Y, Zhang Z (2013) The protective role of resveratrol against arsenic trioxide-induced cardiotoxicity. Evid Based Complement Altern Med 2013:407839. https://doi.org/10.1155/2013/407839
Zhang X, Hu B, Sun Y, Huang X, Cheng J, Huang A, Zeng H, Qiu S, Cao Y, Fan J, Zhou J, Yang XJC, Medicine t (2021) Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF-kB signaling pathways synergistically. Clin Transl Med 11(2):e335. https://doi.org/10.1002/ctm2.335
Zhang X, Hu B, Sun YF, Huang XW, Cheng JW, Huang A, Zeng HY, Qiu SJ, Cao Y, Fan J, Zhou J, Yang XR (2021c) Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF-kB signaling pathways synergistically. Clin Transl Med 11(2):e335. https://doi.org/10.1002/ctm2.335
Zhang XW, Yan XJ, Zhou ZR, Yang FF, Wu ZY, Sun HB, Liang WX, Song AX, Lallemand-Breitenbach V, Jeanne M, Zhang QY, Yang HY, Huang QH, Zhou GB, Tong JH, Zhang Y, Wu JH, Hu HY, de The H, Chen SJ, Chen Z (2010) Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science 328(5975):240–243. https://doi.org/10.1126/science.1183424
Zhang Z, Zhang S, Zhang F, Zhang Q, Wei H, Xiu R, Zhao Y, Sui M (2023) Clinical indicators of hepatotoxicity in newly diagnosed acute promyelocytic leukemia patients undergoing arsenic trioxide treatment. Biol Trace Elem Resdoi. https://doi.org/10.1007/s12011-023-03676-2
Zhao WL, Chen SJ, Shen Y, Xu L, Cai X, Chen GQ, Shen ZX, Chen Z, Wang ZY (2001) Treatment of acute promyelocytic leukemia with arsenic trioxide: clinical and basic studies. Leuk Lymphoma 42(6):1265–1273. https://doi.org/10.3109/10428190109097751
Zhao X, Feng T, Chen H, Shan H, Zhang Y, Lu Y, Yang B (2008a) Arsenic trioxide-induced apoptosis in H9c2 cardiomyocytes: Implications in cardiotoxicity. Basic Clin Pharmacol Toxicol 102(5):419–425. https://doi.org/10.1111/j.1742-7843.2007.00150.x
Zhao XY, Li GY, Liu Y, Chai LM, Chen JX, Zhang Y, Du ZM, Lu YJ, Yang BF (2008b) Resveratrol protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo. Br J Pharmacol 154(1):105–113. https://doi.org/10.1038/bjp.2008.81
Zhao Y, Zang G, Yin T, Ma X, Zhou L, Wu L, Daniel R, Wang Y, Qiu J, Wang G (2021) A novel mechanism of inhibiting in-stent restenosis with arsenic trioxide drug-eluting stent: enhancing contractile phenotype of vascular smooth muscle cells via YAP pathway. Bioact Mater 6(2):375–385. https://doi.org/10.1016/j.bioactmat.2020.08.018
Zhao Z, Li J, Zheng B, Liang Y, Shi J, Zhang J, Han X, Chu L, Chu X, Gao Y (2020) Ameliorative effects and mechanism of crocetin in arsenic trioxide-induced cardiotoxicity in rats. Mol Med Rep 22(6):5271–5281. https://doi.org/10.3892/mmr.2020.11587
Zheng B, Yang Y, Li J, Li J, Zuo S, Chu X, Xu S, Ma D, Chu L (2021) Magnesium isoglycyrrhizinate alleviates arsenic trioxide-induced cardiotoxicity: contribution of Nrf2 and TLR4/NF-κB signaling pathway. Drug Des Dev Ther 15:543–556. https://doi.org/10.2147/dddt.S296405
Zheng CY, Lam SK, Li YY, Fong BM, Mak JC, Ho JC (2013) Combination of arsenic trioxide and chemotherapy in small cell lung cancer. Lung Cancer 82(2):222–230. https://doi.org/10.1016/j.lungcan.2013.08.022
Zheng Y, Zhou M, Ye A, Li Q, Bai Y, Zhang Q (2010) The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells. World J Surg Oncol 8:31. https://doi.org/10.1186/1477-7819-8-31
Zhou C, Boggess JF, Bae-Jump V, Gehrig PA (2007) Induction of apoptosis and inhibition of telomerase activity by arsenic trioxide (As2O3) in endometrial carcinoma cells. Gynecol Oncol 105(1):218–222. https://doi.org/10.1016/j.ygyno.2006.11.027
Zhou J, Meng R, Sui X, Meng L, Jia J, Yang B (2005) Effects of administration styles of arsenic trioxide on intracellular arsenic concentration, cell differentiation and apoptosis. Haematologica 90(9):1277. https://doi.org/10.1002/ajh.25271
Zhou J, Meng R, Sui XH, Meng L, Yang BF (2006) Effects of arsenic trioxide administration styles on leukocytosis. Chin Med Sci J 21(2):111–114
Zhou J, Tan SH, Nicolas V, Bauvy C, Yang ND, Zhang JB, Xue Y, Codogno P, Shen HM (2013) Activation of lysosomal function in the course of autophagy via mTORC1 suppression and autophagosome-lysosome fusion. Cell Res 23(4):508–523. https://doi.org/10.1038/cr.2013.11
Zhou J, Zhang Y, Li J, Li X, Hou J, Zhao Y, Liu X, Han X, Hu L, Wang S, Zhao Y, Zhang Y, Fan S, Lv C, Li L, Zhu L (2010) Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia. Blood 115(9):1697–1702. https://doi.org/10.1182/blood-2009-07-230805
Zhu HH, Qin YZ, Zhang ZL, Liu YJ, Wen LJ, You MJ, Zhang C, Such E, Luo H, Yuan HJ, Zhou HS, Liu HX, Xu R, Li J, Li JH, Hao JP, Jin J, Yu L, Zhang JY, Liu LP, Zhang LP, Huang RB, Shen SH, Gao SJ, Wang W, Yan XJ, Zhang XY, Du X, Chu XX, Yu YF, Wang Y, Mi YC, Lu Y, Cai Z, Su Z, Taussig DC, MacMahon S, Ball ED, Wang HY, Welch JS, Yin CC, Borthakur G, Sanz MA, Kantarjian HM, Huang JY, Hu J, Chen SN (2023) A global study for acute myeloid leukemia with RARG rearrangement. Blood Adv 7(13):2972–2982. https://doi.org/10.1182/bloodadvances.2022008364
Zhu HH, Wu DP, Jin J, Li JY, Ma J, Wang JX, Jiang H, Chen SJ, Huang XJ (2013) Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol 31(33):4215–4221. https://doi.org/10.1200/JCO.2013.48.8312
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This work is supported by the National Natural Science Foundation of China (No. 81903683) and the Startup Fund for Excellent Researchers at Xuzhou Medical University (No. D2018013).
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Yan, M., Wang, H., Wei, R. et al. Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date. Arch. Pharm. Res. 47, 249–271 (2024). https://doi.org/10.1007/s12272-023-01481-y
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DOI: https://doi.org/10.1007/s12272-023-01481-y