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Induced Cell Death as a Possible Pathway of Antimutagenic Action

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Bulletin of Experimental Biology and Medicine Aims and scope

The existing concepts of antimutagenesis are briefly reviewed. Published reports on antimutagenic and proapoptotic properties of some polyphenols and compounds of other chemical groups obtained in representative in vitro and in vivo experiments on eukaryotic test systems are discussed. The relationships between the antimutagenic and proapoptotic properties of the analyzed compounds (naringin, apigenin, resveratrol, curcumin, N-acetylcysteine, etc.) are considered in favor of the hypothesis on induced cell death as an antimutagenic tool.

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References

  1. Durnev AD. Antimutagenesis and antimutagens. Human Physiology. 2018;44(3):336-355.

    Article  CAS  Google Scholar 

  2. Durnev AD. Mutagens and antimutagens in food. Russ. J. Genetics. 1997;33(2):117-127.

    CAS  Google Scholar 

  3. Pligina KL, Zhanataev AK, Kulakova AV, Chaika ZV, Durnev AD. Influence of acetylcysteine on cytogenetic effects of etoposide in mouse oocytes. Russ. J. Genetics. 2016;52(2):188- 193.

    Article  CAS  Google Scholar 

  4. Puzakov KK, Durnova NA, Ryzhenkova IG. Modern ideas about the effect of exogenous antioxidants on the growth of malignant tumors. Obzory po Klin. Farmakol. Lek. Ter. 2019;17(2):29-33. Russian.

    Article  Google Scholar 

  5. Abraham SK, Khandelwal N, Hintzsche H, Stopper H. Antigenotoxic effects of resveratrol: assessment of in vitro and in vivo response. Mutagenesis. 2016;31(1):27-33. doi: https://doi.org/10.1093/mutage/gev048

    Article  CAS  PubMed  Google Scholar 

  6. Agarwal C, Sharma Y, Agarwal R. Anticarcinogenic effect of a polyphenolic fraction isolated from grape seeds in human prostate carcinoma DU145 cells: modulation of mitogenic signaling and cell-cycle regulators and induction of G1 arrest and apoptosis. Mol. Carcinog. 2000;28(3):129-138.

    Article  CAS  Google Scholar 

  7. Ali F, Rahul Naz F, Jyoti S, Siddique YH. Protective effect of apigenin against N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in albino rats. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2014;767:13-20. doi: https://doi.org/10.1016/j.mrgentox.2014.04.006

    Article  CAS  PubMed  Google Scholar 

  8. Alvarez-González I, Madrigal-Bujaidar E, Dorado V, Espinosa-Aguirre JJ. Inhibitory effect of naringin on the micronuclei induced by ifosfamide in mouse, and evaluation of its modulatory effect on the Cyp3a subfamily. Mutat. Res. 2001;480- 481:171-178. doi: 10.1016/s0027-5107(01)00197-x

  9. Alvarez-González I, Madrigal-Bujaidar E, Martino-Roaro L, Espinosa-Aguirre JJ. Antigenotoxic and antioxidant effect of grapefruit juice in mice treated with daunorubicin. Toxicol. Lett. 2004;152(3):203-211. doi: https://doi.org/10.1016/j.toxlet.2004.04.034

    Article  CAS  PubMed  Google Scholar 

  10. Alvarez-González I, Madrigal-Bujaidar E, Sánchez-García VY. Inhibitory effect of grapefruit juice on the genotoxic damage induced by ifosfamide in mouse. Plant Foods Hum. Nutr. 2010;65(4):369-373. doi: https://doi.org/10.1007/s11130-010-0193-1

    Article  CAS  PubMed  Google Scholar 

  11. Alvarez-Gonzalez I, Mojica R, Madrigal-Bujaidar E, Camacho-Carranza R, Escobar-García D, Espinosa-Aguirre JJ. The antigenotoxic effects of grapefruit juice on the damage induced by benzo(a)pyrene and evaluation of its interaction with hepatic and intestinal Cytochrome P450 (Cyp) 1a1. Food Chem. Toxicol. 2011;49(4):807-811. doi: https://doi.org/10.1016/j.fct.2010.11.047

    Article  CAS  PubMed  Google Scholar 

  12. Amara-Mokrane YA, Lehucher-Michel MP, Balansard G, Duménil G, Botta A. Protective effects of alpha-hederin, chlorophyllin and ascorbic acid towards the induction of micronuclei by doxorubicin in cultured human lymphocytes. Mutagenesis. 1996;11(2):161-167. doi: https://doi.org/10.1093/mutage/11.2.161

    Article  CAS  PubMed  Google Scholar 

  13. Anter J, Romero-Jiménez M, Fernández-Bedmar Z, Villatoro-Pulido M, Analla M, Alonso-Moraga A, Muñoz-Serrano A. Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol, and protocatechuic acid. J. Med. Food. 2011;14(3):276-283. doi: https://doi.org/10.1089/jmf.2010.0139

    Article  CAS  PubMed  Google Scholar 

  14. Asensi M, Ortega A, Mena S, Feddi F, Estrela JM. Natural polyphenols in cancer therapy. Crit. Rev. Clin. Lab. Sci. 2011;48(5-6):197-216. doi: https://doi.org/10.3109/10408363.2011.631268

    Article  CAS  PubMed  Google Scholar 

  15. Attia SM. Influence of resveratrol on oxidative damage in genomic DNA and apoptosis induced by cisplatin. Mutat. Res. 2012;741(1-2):22-31. doi: https://doi.org/10.1016/j.mrgentox.2011.10.008

    Article  CAS  PubMed  Google Scholar 

  16. Balakrishnan S, Vellaichamy L, Menon VP, Manoharan S. Antigenotoxic effects of curcumin and piperine alone or in combination against 7,12-dimethylbenz(a)anthracene induced genotoxicity in bone marrow of golden Syrian hamsters. Toxicol. Mech. Methods. 2008;18(9):691-696. doi: https://doi.org/10.1080/15376510701781520

    Article  CAS  PubMed  Google Scholar 

  17. Banjerdpongchai R, Wudtiwai B, Khawon P. Induction of human hepatocellular carcinoma HepG2 cell apoptosis by naringin. Asian Pac. J. Cancer Prev. 2016;17(7):3289-3294.

    PubMed  Google Scholar 

  18. Basu AK. DNA damage, mutagenesis and cancer. Int. J. Mol. Sci. 2018;19(4):970. doi: https://doi.org/10.3390/ijms19040970

    Article  CAS  PubMed Central  Google Scholar 

  19. Baumeister P, Huebner T, Reiter M, Schwenk-Zieger S, Harréus U. Reduction of oxidative DNA fragmentation by ascorbic acid, zinc and N-acetylcysteine in nasal mucosa tissue cultures. Anticancer Res. 2009;29(11):4571-4574.

    CAS  PubMed  Google Scholar 

  20. Benzie IF, Choi SW. Antioxidants in food: content, measurement, significance, action, cautions, caveats, and research needs. Adv. Food Nutr. Res. 2014;71:1-53. doi: https://doi.org/10.1016/B978-0-12-800270-4.00001-8

    Article  CAS  PubMed  Google Scholar 

  21. Bhaskar AS, Deb U, Kumar O, Lakshmana Rao PV. Abrin induced oxidative stress mediated DNA damage in human leukemic cells and its reversal by N-acetylcysteine. Toxicol. In Vitro. 2008;22(8):1902-1908. doi: https://doi.org/10.1016/j.tiv.2008.09.013

    Article  CAS  PubMed  Google Scholar 

  22. Blum CA, Xu M, Orner GA, Darío Díaz G, Li Q, Dashwood WM, Bailey GS, Dashwood RH. Promotion versus suppression of rat colon carcinogenesis by chlorophyllin and chlorophyll: modulation of apoptosis, cell proliferation, and beta-catenin/Tcf signaling. Mutat. Res. 2003;523-524:217-223. doi: 10.1016/s0027-5107(02)00338-x

  23. Bokulić A, Garaj-Vrhovac V, Brajsa K, Ethurić K, Glojnarić I, Situm K. The effect of apigenin on cyclophosphamide and doxorubicin genotoxicity in vitro and in vivo. J. Environ. Sci. Health A Tox. Hazard Subst. Environ. Eng. 2011;46(5):526-533. doi: https://doi.org/10.1080/10934529.2011.551744

    Article  CAS  Google Scholar 

  24. Bonechi C, Martini S, Magnani A, Rossi C. Stacking interaction study of trans-resveratrol (trans-3,5,4’-trihydroxystilbene) in solution by nuclear magnetic resonance and fourier transform infrared spectroscopy. Magn. Reson. Chem. 2008;46(7):625-629. doi: https://doi.org/10.1002/mrc.2217

    Article  CAS  PubMed  Google Scholar 

  25. Budhraja A, Gao N, Zhang Z, Son Y.O, Cheng S, Wang X, Ding S, Hitron A, Chen G, Luo J, Shi X. Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo. Mol. Cancer Ther. 2012;11(1):132-142. doi: https://doi.org/10.1158/1535-7163.MCT-11-0343

    Article  CAS  PubMed  Google Scholar 

  26. Cai L, Wu H, Tu C, Wen X, Zhou B. Naringin inhibits ovarian tumor growth by promoting apoptosis: An in vivo study. Oncol. Lett. 2018;16(1):59-64. doi: https://doi.org/10.3892/ol.2018.8611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cao X, Liu B, Cao W, Zhang W, Zhang F, Zhao H, Meng R, Zhang L, Niu R, Hao X, Zhang B. Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells. Chin. J. Cancer Res. 2013;25(2):212-222. doi: https://doi.org/10.3978/j.issn.1000-9604.2013.04.01

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cariño-Cortés R, Alvarez-González I, Martino-Roaro L, Madrigal- Bujaidar E. Effect of naringin on the DNA damage induced by daunorubicin in mouse hepatocytes and cardiocytes. Biol. Pharm. Bull. 2010;33(4):697-701. doi: https://doi.org/10.1248/bpb.33.697

    Article  Google Scholar 

  29. Chakrabarty S, Ganguli A, Das A, Nag D, Chakrabarti G. Epigallocatechin-3-gallate shows anti-proliferative activity in HeLa cells targeting tubulin-microtubule equilibrium. Chem. Biol. Interact. 2015;242:380-389. doi: https://doi.org/10.1016/j.cbi.2015.11.004

    Article  CAS  PubMed  Google Scholar 

  30. Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ. Mol. Mutagen. 2017;58(5):235-263. doi: https://doi.org/10.1002/em.22087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen Z, Yuan Q, Xu G, Chen H, Lei H, Su J. Effects of quercetin on proliferation and H2O2-induced apoptosis of intestinal porcine enterocyte cells. Molecules. 2018;23(8):2012. doi: https://doi.org/10.3390/molecules23082012

    Article  CAS  PubMed Central  Google Scholar 

  32. Chu H, Li M, Wang X. Capsaicin induces apoptosis and autophagy in human melanoma cells. Oncol. Lett. 2019;17(6): 4827-4834. doi: https://doi.org/10.3892/ol.2019.10206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cristóbal-Luna JM, Álvarez-González I, Madrigal-Bujaidar E, Chamorro-Cevallos G. Grapefruit and its biomedical, antigenotoxic and chemopreventive properties. Food Chem. Toxicol. 2018;112):224-234. doi: 10.1016/j.fct.2017.12.038

  34. Curti V, Di Lorenzo A, Dacrema M, Xiao J, Nabavi SM, Daglia M. In vitro polyphenol effects on apoptosis: an update of literature data. Semin. Cancer Biol. 2017;46:119-131. doi: https://doi.org/10.1016/j.semcancer.2017.08.005

    Article  CAS  PubMed  Google Scholar 

  35. D Epiro GF, Semprebon SC, Niwa AM, Marcarini JC, Mantovani MS. Roles of chlorophyllin in cell proliferation and the expression of apoptotic and cell cycle genes in HB4a nontumor breast cells. Toxicol. Mech. Methods. 2016;26(5):348- 354. doi: 10.3109/15376516.2016.1172692

  36. Dashwood RH, Xu M, Orner GA, Horio DT. Colonic cell proliferation, apoptosis and aberrant crypt foci development in rats given 2-amino-3-methylimidaz. Eur. J. Cancer Prev. 2001;10(2):139-145. doi: https://doi.org/10.1097/00008469-200104000-00004

    Article  CAS  PubMed  Google Scholar 

  37. De Flora S, Izzotti A, D’Agostini F, Balansky RM. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related endpoints. Carcinogenesis. 2001;22(7):999-1013. doi: https://doi.org/10.1093/carcin/22.7.999

    Article  PubMed  Google Scholar 

  38. Deng J, Liu AD, Hou GQ, Zhang X, Ren K, Chen XZ, Li SSC, Wu YS, Cao X. N-acetylcysteine decreases malignant characteristics of glioblastoma cells by inhibiting Notch2 signaling. J. Exp. Clin. Cancer Res. 2019;38(1):2. doi: https://doi.org/10.1186/s13046-018-1016-8

    Article  PubMed  PubMed Central  Google Scholar 

  39. Díaz GD, Li Q, Dashwood RH. Caspase-8 and apoptosis-inducing factor mediate a cytochrome c-independent pathway of apoptosis in human colon cancer cells induced by the dietary phytochemical chlorophyllin. Cancer Res. 2003;63(6):1254-1261.

    PubMed  Google Scholar 

  40. Diaz-Gerevini GT, Repossi G, Dain A, Tarres MC, Das UN, Eynard AR. Beneficial action of resveratrol: how and why? Nutrition. 2016;32(2):174-178. doi: https://doi.org/10.1016/j.nut.2015.08.017

    Article  CAS  PubMed  Google Scholar 

  41. Ding L, Gao X, Hu J, Yu S. (-)Epigallocatechin-3-gallate attenuates anesthesia-induced memory deficit in young mice via modulation of nitric oxide expression. Mol. Med. Rep. 2018;18(6):4813-4820. doi: https://doi.org/10.3892/mmr.2018.9548

    Article  CAS  Google Scholar 

  42. Elshaer M, Chen Y, Wang XJ, Tang X. Resveratrol: An overview of its anti-cancer mechanisms. Life Sci. 2018;207:340- 349. doi: 10.1016/j.lfs.2018.06.028

  43. Eluka-Okoludoh E, Ewunkem A.J, Thorpe S, Blanchard A, Muganda P. Diepoxybutane-induced apoptosis is mediated through the ERK1/2 pathway. Hum. Exp. Toxicol. 2018; 37(10):1080-1091. doi: https://doi.org/10.1177/0960327118755255

    Article  CAS  PubMed  Google Scholar 

  44. Erdogan S, Doganlar O, Doganlar ZB, Serttas R, Turkekul K, Dibirdik I, Bilir A. The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling. Life Sci. 2016;162:77-86. doi: https://doi.org/10.1016/j.lfs.2016.08.019

    Article  CAS  PubMed  Google Scholar 

  45. Erdogan S, Doganlar O, Doganlar ZB, Turkekul K. Naringin sensitizes human prostate cancer cells to paclitaxel therapy. Prostate Int. 2018;6(4):126-135. doi: https://doi.org/10.1016/j.prnil.2017.11.001

    Article  PubMed  Google Scholar 

  46. Fang D, Xiong Z, Xu J, Yin J, Luo R. Chemopreventive mechanisms of galangin against hepatocellular carcinoma: a review. Biomed. Pharmacother. 2019;109:2054-2061. doi: https://doi.org/10.1016/j.biopha.2018.09.154

    Article  CAS  PubMed  Google Scholar 

  47. Fang J, Bao YY, Zhou SH, Fan J. Apigenin inhibits the proliferation of adenoid cystic carcinoma via suppression of glucose transporter-1. Mol. Med. Rep. 2015;12(5):6461-6466. doi: https://doi.org/10.3892/mmr.2015.4233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Farhood B, Mortezaee K, Goradel H, Khanlarkhani N, Salehi E, Nashtaei MS, Najafi M, Sahebkar A. Curcumin as an anti-inflammatory agent: implications to radiotherapy and chemotherapy. J. Cell. Physiol. 2019;234(5):5728-5740. doi: https://doi.org/10.1002/jcp.27442

    Article  CAS  PubMed  Google Scholar 

  49. Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV, Rudka T, Bartoli D, Polishuck RS, Danial NN, De Strooper B, Scorrano L. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell. 2006;126(1):177-189. doi: https://doi.org/10.1016/j.cell.2006.06.025

    Article  CAS  PubMed  Google Scholar 

  50. Ganaie MA, Jan BL, Khan TH, Alharthy KM, Sheikh IA. The protective effect of naringenin on oxaliplatin-induced genotoxicity in mice. Chem. Pharm. Bull. (Tokyo). 2019;67(5):433-438. doi: 10.1248/cpb.c18-00809

  51. García-Lafuente A, Guillamón E, Villares A, Rostagno MA, Martínez JA. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm. Res. 2009;58(9):537-552. doi: https://doi.org/10.1007/s00011-009-0037-3

    Article  CAS  PubMed  Google Scholar 

  52. García-Rodríguez MC, López-Santiago V, Altamirano-Lozano M. Effect of chlorophyllin on chromium trioxide-induced micronuclei in polychromatic erythrocytes in mouse peripheral blood. Mutat. Res. 2001;496(1-2):145-151. doi: https://doi.org/10.1016/s1383-5718(01)00225-x

    Article  PubMed  Google Scholar 

  53. García-Rodríguez Mdel C, Carvente-Juárez MM, Altamirano-Lozano MA. Antigenotoxic and apoptotic activity of green tea polyphenol extracts on hexavalent chromium-induced DNA damage in peripheral blood of CD-1 mice: analysis with differential acridine orange/ethidium bromide staining. Oxid. Med. Cell. Longev. 2013;2013:486419. doi: https://doi.org/10.1155/2013/486419

    Article  CAS  PubMed  Google Scholar 

  54. Goldar S, Khaniani MS, Derakhshan S.M, Baradaran B. Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac. J. Cancer Prev. 2015;16(6):2129-2244. doi: https://doi.org/10.7314/apjcp.2015.16.6.2129

  55. Grossi M.R, Berni A, Pepe G, Filippi S, Mosesso P, Shivnani AA, Papeschi C, Natarajan AT, Palitti F. A comparative study of the anticlastogenic effects of chlorophyllin on N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz (alpha) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo. Toxicol. Lett. 2012;214(3):235-242. doi: https://doi.org/10.1016/j.toxlet.2012.08.023

  56. Gupta S, Afaq F, Mukhtar H. Involvement of nuclear factorkappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene. 2002;21(23):3727-3738. doi: https://doi.org/10.1038/sj.onc.1205474

    Article  CAS  PubMed  Google Scholar 

  57. Gurbuz N, Ozkul A, Burgaz S. Effects of vitamin C and Nacetylcysteine against cyclophosphamide-induced genotoxicity in exfoliated bladder cells of mice in vivo. J. BUON. 2009;14(4):647-652.

    CAS  PubMed  Google Scholar 

  58. Hassan FU, Rehman MS, Khan MS, Ali MA, Javed A, Nawaz A, Yang C. Curcumin as an alternative epigenetic modulator: mechanism of action and potential effects. Front. Genet. 2019;10:514. doi: https://doi.org/10.3389/fgene.2019.00514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hernández-Ceruelos A, Madrigal-Bujaidar E, de la Cruz C. Inhibitory effect of chamomile essential oil on the sister chromatid exchanges induced by daunorubicin and methyl methanesulfonate in mouse bone marrow. Toxicol. Lett. 2002;135(1- 2):103-110. doi: 10.1016/s0378-4274(02)00253-9

  60. Hider RC, Liu ZD, Khodr HH. Metal chelation of polyphenols. Methods Enzymol. 2001;335:190-203. doi: https://doi.org/10.1016/s0076-6879(01)35243-6

    Article  CAS  PubMed  Google Scholar 

  61. Huang FM, Chang YC, Lee SS, Ho YC, Yang ML, Lin HW, Kuan YH. Bisphenol A exhibits cytotoxic or genotoxic potential via oxidative stress-associated mitochondrial apoptotic pathway in murine macrophages. Food Chem. Toxicol. 2018;122:215-224. doi: https://doi.org/10.1016/j.fct.2018.09.078

    Article  CAS  PubMed  Google Scholar 

  62. Hussain SA, Sulaiman AA, Balch C, Chauhan H, Alhadidi QM, Tiwari AK. Natural polyphenols in cancer chemo- resistance. Nutr. Cancer. 2016;68(6):879-891. doi: https://doi.org/10.1080/01635581.2016.1192201

    Article  CAS  PubMed  Google Scholar 

  63. Izquierdo-Vega JA, Morales-González JA, SánchezGutiérrez M, Betanzos-Cabrera G, Sosa-Delgado SM, Sumaya-Martínez MT, Morales-González Á, Paniagua-Pérez R, Madrigal- Bujaidar E, Madrigal-Santillán E. Evidence of some natural products with antigenotoxic effects. Part 1: Fruits and polysaccharides. Nutrients. 2017;9(2):102. doi: 10.3390/nu9020102

  64. Kampa M, Nifli A.P, Notas G, Castanas E. Polyphenols and cancer cell growth. Rev. Physiol. Biochem. Pharmacol. 2007;159:79-113. doi: https://doi.org/10.1007/112_2006_0702

    Article  CAS  PubMed  Google Scholar 

  65. Kaur IP, Deol PK, Kondepudi KK, Bishnoi M. Anticancer potential of ginger: mechanistic and pharmaceutical aspects. Curr. Pharm. Des. 2016;22(27):4160-4172. doi: https://doi.org/10.2174/1381612822666160608115350

    Article  CAS  PubMed  Google Scholar 

  66. Keshava C, Keshava N, Whong WZ, Nath J, Ong TM. Inhibition of methotrexate-induced chromosomal damage by vanillin and chlorophyllin in V79 cells. Teratog. Carcinog. Mutagen. 1997-1998;17(6):313-326.

    Article  CAS  Google Scholar 

  67. Khan H, Ullah H, Castilho PCMF, Gomila AS, D’Onofrio G, Filosa R, Wang F, Nabavi S.M, Daglia M, Silva AS, Rengasamy KRR, Ou J, Zou X, Xiao J, Cao H. Targeting NF-kappaB signaling pathway in cancer by dietary polyphenols. Crit. Rev. Food Sci. Nutr. 2020;60(16):2790-2800. doi: https://doi.org/10.1080/10408398.2019.1661827

    Article  CAS  PubMed  Google Scholar 

  68. Ko JH, Sethi G, Um JY, Shanmugam MK, Arfuso F, Kumar AP, Bishayee A, Ahn KS. The role of resveratrol in cancer therapy. Int. J. Mol. Sci. 2017;18(12):2589. doi: https://doi.org/10.3390/ijms18122589

    Article  CAS  PubMed Central  Google Scholar 

  69. Kou X, Chen N. Resveratrol as a natural autophagy regulator for prevention and treatment of Alzheimer’s disease. Nutrients. 2017;9(9):927. doi: https://doi.org/10.3390/nu9090927

    Article  CAS  PubMed Central  Google Scholar 

  70. Lafon C, Mathieu C, Guerrin M, Pierre O, Vidal S, Valette A. Transforming growth factor beta 1-induced apoptosis in human ovarian carcinoma cells: protection by the antioxidant N-acetylcysteine and bcl-2. Cell Growth Differ. 1996;7(8):1095-1104.

    CAS  PubMed  Google Scholar 

  71. Lee Y, Sung B, Kang YJ, Kim DH, Jang JY, Hwang SY, Kim M, Lim HS, Yoon JH, Chung HY, Kim ND. Apigenininduced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells. Int. J. Oncol. 2014;44(5):1599-1606. doi: https://doi.org/10.3892/ijo.2014.2339

    Article  CAS  PubMed  Google Scholar 

  72. Lee YJ, Hwang IS, Lee YJ, Lee CH, Kim SH, Nam HS, Choi YJ, Lee SH. Knockdown of Bcl-xL enhances growthinhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells. J. Korean Med. Sci. 2014;29(11):1464-1472. doi: https://doi.org/10.3346/jkms.2014.29.11.1464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lewandowska H, Kalinowska M, Lewandowski W, Stępkowski TM, Brzóska K. The role of natural polyphenols in cell signaling and cytoprotection against cancer development. J. Nutr. Biochem. 2016;32:1-19. doi: https://doi.org/10.1016/j.jnutbio.2015.11.006

    Article  CAS  PubMed  Google Scholar 

  74. Li H, Yang B, Huang J, Xiang T, Yin X, Wan J, Luo F, Zhang L, Li H, Ren G. Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting β-catenin signaling pathway. Toxicol. Lett. 2013;220(3):219-228. doi: https://doi.org/10.1016/j.toxlet.2013.05.006

    Article  CAS  PubMed  Google Scholar 

  75. Li L, Hai J, Li Z, Zhang Y, Peng H, Li K, Weng X. Resveratrol modulates autophagy and NF-κB activity in a murine model for treating non-alcoholic fatty liver disease. Food Chem. Toxicol. 2014;63:166-173. doi: https://doi.org/10.1016/j.fct.2013.08.036

    Article  CAS  PubMed  Google Scholar 

  76. Lim YJ, Kim JH, Pan JH, Kim JK, Park TS, Kim YJ, Lee JH, Kim JH. Naringin protects pancreatic β-cells against oxidative stress-induced apoptosis by inhibiting both intrinsic and extrinsic pathways in insulin-deficient diabetic mice. Mol. Nutr. Food Res. 2018;62(5). doi: 10.1002/mnfr.201700810

  77. Lin JK, Liang YC, Lin-Shiau SY. Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem. Pharmacol. 1999;58(6):911-915. doi: https://doi.org/10.1016/s0006-2952(99)00112-4

    Article  CAS  PubMed  Google Scholar 

  78. Liu JS, Chiang TH, Wang JS, Lin LJ, Chao WC, Inbaraj BS, Lu JF, Chen BH. Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides. J. Cell. Mol. Med. 2015;19(7):1697-1709. doi: https://doi.org/10.1111/jcmm.12546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J. Nutr. 2004;134(12, Suppl):3479S-3485S. doi: 10.1093/jn/134.12.3479S

  80. Liu Y, Liu K, Wang N, Zhang H. N-acetylcysteine induces apoptosis via the mitochondria-dependent pathway but not via endoplasmic reticulum stress in H9c2 cells. Mol. Med. Rep. 2017;16(5):6626-6633. doi: https://doi.org/10.3892/mmr.2017.7442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Maatouk M, Mustapha N, Mokdad-Bzeouich I, Chaaban H, Ioannou I, Ghedira K, Ghoul M, Chekir-Ghedira L. Heated naringin mitigate the genotoxicity effect of Mitomycin C in BALB/c mice through enhancing the antioxidant status. Biomed. Pharmacother. 2018;97:1417-1423. doi: https://doi.org/10.1016/j.biopha.2017.11.027

    Article  CAS  PubMed  Google Scholar 

  82. Martino R, Arcos ML, Alonso R, Sülsen V, Cremaschi G, Anesini C. Polyphenol-rich fraction from Larrea divaricata and its main flavonoid quercetin-3-methyl ether induce apoptosis in lymphoma cells through nitrosative stress. Phytother. Res. 2016;30(7):1128-1136. doi: https://doi.org/10.1002/ptr.5615

    Article  CAS  PubMed  Google Scholar 

  83. Masuelli L, Benvenuto M, Mattera R, Di Stefano E, Zago E, Taffera G, Tresoldi I, Giganti MG, Frajese GV, Berardi G, Modesti A, Bei R. In vitro and in vivo anti-tumoral effects of the flavonoid apigenin in malignant mesothelioma. Front. Pharmacol. 2017;8:373. doi: https://doi.org/10.3389/fphar.2017.00373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Masuelli L, Marzocchella L, Focaccetti C, Tresoldi I, Palumbo C, Izzi V, Benvenuto M, Fantini M, Lista F, Tarantino U, Modesti A, Galvano F, Bei R. Resveratrol and diallyl disulfide enhance curcumin-induced sarcoma cell apoptosis. Front. Biosci. (Landmark Ed). 2012;17:498-508. doi: 10.2741/3940

  85. Ming H, Chuang Q, Jiashi W, Bin L, Guangbin W, Xianglu J. Naringin targets Zeb1 to suppress osteosarcoma cell proliferation and metastasis. Aging (Albany NY). 2018;10(12):4141-4151. doi: 10.18632/aging.101710

  86. Miyata M, Takano H, Guo LQ, Nagata K, Yamazoe Y. Grapefruit juice intake does not enhance but rather protects against aflatoxin B1-induced liver DNA damage through a reduction in hepatic CYP3A activity. Carcinogenesis. 2004;25(2):203-209. doi: https://doi.org/10.1093/carcin/bgg194

    Article  CAS  PubMed  Google Scholar 

  87. Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, Siegelin MD, Fimognari C, Kumar NB, Dou QP, Yang H, Samadi AK, Russo GL, Spagnuolo C, Ray SK, Chakrabarti M, Morre JD, Coley HM, Honoki K, Fujii H, Georgakilas AG, Amedei A, Niccolai E, Amin A, Ashraf SS, Helferich WG, Yang X, Boosani CS, Guha G, Bhakta D, Ciriolo MR, Aquilano K, Chen S, Mohammed SI, Keith WN, Bilsland A, Halicka D, Nowsheen S, Azmi AS. Broad targeting of resistance to apoptosis in cancer. Semin. Cancer Biol. 2015;35(Suppl):S78-S103. doi: 10.1016/j.semcancer.2015.03.001

  88. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25(3):486-541. doi: 10.1038/s41418-017-0012-4

  89. Monti D, Sotgia F, Whitaker-Menezes D, Tuluc M, Birbe R, Berger A, Lazar M, Cotzia P, Draganova-Tacheva R, Lin Z, Domingo-Vidal M, Newberg A, Lisanti MP, Martinez-Outschoorn U. Pilot study demonstrating metabolic and anti-pro-liferative effects of in vivo anti-oxidant supplementation with N-acetylcysteine in breast cancer. Semin. Oncol. 2017; 44(3):226-232. doi: https://doi.org/10.1053/j.seminoncol.2017.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mortezaee K, Salehi E, Mirtavoos-Mahyari H, Motevaseli E, Najafi M, Farhood B, Rosengren RJ, Sahebkar A. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J. Cell. Physiol. 2019;234(8):12537-12550. doi: https://doi.org/10.1002/jcp.28122

    Article  CAS  PubMed  Google Scholar 

  91. Mostafapour Kandelous H, Salimi M, Khori V, Rastkari N, Amanzadeh A, Salimi M. Mitochondrial apoptosis induced by Chamaemelum nobile extract in breast cancer cells. Iran J. Pharm. Res. 2016;15(Suppl):197-204.

    PubMed  PubMed Central  Google Scholar 

  92. Nagini S, Palitti F, Natarajan AT. Chemopreventive potential of chlorophyllin: a review of the mechanisms of action and molecular targets. Nutr. Cancer. 2015;67(2):203-211. doi: https://doi.org/10.1080/01635581.2015.990573

    Article  CAS  PubMed  Google Scholar 

  93. Neveu V, Perez-Jiménez J, Vos F, Crespy V, du Chaffaut L, Mennen L, Knox C, Eisner R, Cruz J, Wishart D, Scalbert A. Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford). 2010;2010: bap024. doi: 10.1093/database/bap024

  94. Niedzwiecki A, Roomi MW, Kalinovsky T, Rath M. Antican-cer Efficacy of Polyphenols and Their Combinations. Nutrients. 2016;8(9):552. doi: https://doi.org/10.3390/nu8090552

    Article  CAS  PubMed Central  Google Scholar 

  95. Nikseresht M, Kamali AM, Rahimi HR, Delaviz H, Toori MA, Kashani IR, Mahmoudi R. The hydroalcoholic extract of Matricaria chamomilla suppresses migration and invasion of human breast cancer MDA-MB-468 and MCF-7 cell lines. Pharmacognosy Res. 2017;9(1):87-95. doi: 10.4103/0974-8490.199778

  96. Oršolić N, Benković V, Lisičić D, Dikić D, Erhardt J, Knežević AH. Protective effects of propolis and related polyphenolic/flavonoid compounds against toxicity induced by irinotecan. Med. Oncol. 2010;27(4):1346-1358. doi: https://doi.org/10.1007/s12032-009-9387-5

    Article  CAS  PubMed  Google Scholar 

  97. Oršolić N, Gajski G, Garaj-Vrhovac V, Dikić D, Prskalo ZŠ, Sirovina D. DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice. Eur. J. Pharmacol. 2011;656(1-3):110-118. doi: https://doi.org/10.1016/j.ejphar.2011.01.021

    Article  CAS  PubMed  Google Scholar 

  98. Papież MA. The influence of curcumin and (-)-epicatechin on the genotoxicity and myelosuppression induced by etoposide in bone marrow cells of male rats. Drug Chem. Toxicol. 2013;36(1):93-101. doi: https://doi.org/10.3109/01480545.2012.726626

    Article  CAS  PubMed  Google Scholar 

  99. Patar AK, Sharma A, Syiem D, Bhan S. Chlorophyllin supplementation modulates hyperglycemia-induced oxidative stress and apoptosis in liver of streptozotocin-administered mice. Biofactors. 2018;44(5):418-430. doi: https://doi.org/10.1002/biof.1438

    Article  CAS  PubMed  Google Scholar 

  100. Pérez-Jiménez J, Neveu V, Vos F, Scalbert A. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. Eur. J. Clin. Nutr. 2010;64(Suppl 3):S112-S120. doi: https://doi.org/10.1038/ejcn.2010.221

    Article  CAS  PubMed  Google Scholar 

  101. Prasad S, Gupta SC, Tyagi AK. Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals. Cancer Lett. 2017;387:95-105. doi: https://doi.org/10.1016/j.canlet.2016.03.042

    Article  CAS  PubMed  Google Scholar 

  102. Qanungo S, Uys JD, Manevich Y, Distler AM, Shaner B, Hill EG, Mieyal JJ, Lemasters JJ, Townsend DM, Nieminen AL. N-acetyl-L-cysteine sensitizes pancreatic cancers to gemcitabine by targeting the NFκB pathway. Biomed. Pharmacother. 2014;68(7):855-864. doi: https://doi.org/10.1016/j.biopha.2014.08.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Qanungo S, Wang M, Nieminen AL. N-Acetyl-L-cysteine enhances apoptosis through inhibition of nuclear factor-kappaB in hypoxic murine embryonic fibroblasts. J. Biol. Chem. 2004;279(48):50 455-50 464. doi: 10.1074/jbc.M406749200

  104. Ramesh E, Alshatwi AA. Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells. Food Chem. Toxicol. 2013;51:97-105. doi: https://doi.org/10.1016/j.fct.2012.07.033

    Article  CAS  PubMed  Google Scholar 

  105. Rieber M, Rieber MS. N-Acetylcysteine enhances UV-mediated caspase-3 activation, fragmentation of E2F-4, and apoptosis in human C8161 melanoma: inhibition by ectopic Bcl-2 expression. Biochem. Pharmacol. 2003;65(10):1593-1601. doi: https://doi.org/10.1016/s0006-2952(03)00147-3

    Article  CAS  PubMed  Google Scholar 

  106. Roos WP, Kaina B. DNA damage-induced cell death: from specific DNA lesions to the DNA damage response and apoptosis. Cancer Lett. 2013;332(2):237-248. doi: https://doi.org/10.1016/j.canlet.2012.01.007

    Article  CAS  PubMed  Google Scholar 

  107. Roy M, Chakrabarty S, Sinha D, Bhattacharya RK, Siddiqi M. Anticlastogenic, antigenotoxic and apoptotic activity of epigallocatechin gallate: a green tea polyphenol. Mutat. Res. 2003;523-524:33-41. doi: 10.1016/s0027-5107(02)00319-6

  108. Russo A, Acquaviva R, Campisi A, Sorrenti V, Di Giacomo C, Virgata G, Barcellona ML, Vanella A. Bioflavonoids as antiradicals, antioxidants and DNA cleavage protectors. Cell. Biol. Toxicol. 2000;16(2):91-98. doi: https://doi.org/10.1023/a:1007685909018

    Article  CAS  PubMed  Google Scholar 

  109. Sakr SA, Zoil Mel-S, El-Shafey SS. Ameliorative effect of grapefruit juice on amiodarone-induced cytogenetic and testicular damage in albino rats. Asian Pac. J. Trop. Biomed. 2013;3(7):573-579. doi: https://doi.org/10.1016/S2221-1691(13)60116-1

    Article  PubMed  PubMed Central  Google Scholar 

  110. Sehgal A, Kumar M, Jain M, Dhawan DK. Modulatory effects of curcumin in conjunction with piperine on benzo(a)pyrene-mediated DNA adducts and biotransformation enzymes. Nutr. Cancer. 2013;65(6):885-890. doi: https://doi.org/10.1080/01635581.2013.805421

    Article  CAS  PubMed  Google Scholar 

  111. Seo HS, Jo JK, Ku JM, Choi HS, Choi YK, Woo JK, Kim HI, Kang SY, Lee KM, Nam KW, Park N, Jang BH, Shin YC, Ko SG. Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2- overexpressing BT-474 breast cancer cells. Biosci. Rep. 2015;35(6):e00276. doi: https://doi.org/10.1042/BSR20150165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Seo HS, Ku JM, Choi HS, Woo JK, Jang BH, Go H, Shin YC, Ko SG. Apigenin induces caspase-dependent apoptosis by inhibiting signal transducer and activator of transcription 3 signaling in HER2-overexpressing SKBR3 breast cancer cells. Mol. Med. Rep. 2015;12(2):2977-2984. doi: https://doi.org/10.3892/mmr.2015.3698

    Article  CAS  PubMed  Google Scholar 

  113. Seo HS, Ku JM, Choi HS, Woo JK, Jang BH, Shin YC, Ko SG. Induction of caspase-dependent apoptosis by apigenin by inhibiting STAT3 signaling in HER2-overexpressing MDA-MB-453 breast cancer cells. Anticancer Res. 2014;34(6):2869-2882.

    CAS  PubMed  Google Scholar 

  114. Seong H, Ryu J, Yoo WS, Kim SJ, Han YS, Park JM, Kang SS, Seo SW. Resveratrol ameliorates retinal ischemia/reperfusion injury in C57BL/6J mice via downregulation of caspase-3. Curr. Eye Res. 2017;42(12):1650-1658. doi: https://doi.org/10.1080/02713683.2017.1344713

    Article  CAS  PubMed  Google Scholar 

  115. Serpeloni JM, Almeida MR, Mercadante AZ, Bianchi ML, Antunes LM. Effects of lutein and chlorophyll b on GSH depletion and DNA damage induced by cisplatin in vivo. Hum. Exp. Toxicol. 2013;32(8):828-836. doi: https://doi.org/10.1177/0960327112468911

    Article  CAS  PubMed  Google Scholar 

  116. Serpeloni JM, Batista BL, Angeli JP, Barcelos GR, Bianchi Mde L, Barbosa F Jr, Antunes LM. Antigenotoxic properties of chlorophyll b against cisplatin-induced DNA damage and its relationship with distribution of platinum and magnesium in vivo. J. Toxicol. Environ. Health A. 2013;76(6):345-353. doi: https://doi.org/10.1080/15287394.2012.755485

    Article  CAS  PubMed  Google Scholar 

  117. Serpeloni JM, Grotto D, Aissa AF, Mercadante AZ, Bianchi Mde L, Antunes LM. An evaluation, using the comet assay and the micronucleus test, of the antigenotoxic effects of chlorophyll b in mice. Mutat. Res. 2011;725(1-2):50-56. doi: https://doi.org/10.1016/j.mrgentox.2011.06.009

    Article  CAS  PubMed  Google Scholar 

  118. Shangguan WJ, Zhang YH, Li ZC, Tang LM, Shao J, Li H. Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress- and mitochondrial-mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats. Int. J. Mol. Med. 2017;40(6):1741-1749. doi: https://doi.org/10.3892/ijmm.2017.3160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Shankar S, Singh G, Srivastava RK. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front. Biosci. 2007;12:4839-4854. doi: https://doi.org/10.2741/2432

    Article  CAS  PubMed  Google Scholar 

  120. Sharma NK. Modulation of radiation-induced and mitomycin C-induced chromosome damage by apigenin in human lymphocytes in vitro. J. Radiat. Res. 2013;54(5):789-797. doi: https://doi.org/10.1093/jrr/rrs117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Shati AA. Doxorubicin-induces NFAT/Fas/FasL cardiac apoptosis in rats through activation of calcineurin and P38 MAPK and inhibition of mTOR signalling pathways. Clin. Exp. Pharmacol. Physiol. 2020;47(4):660-676. doi: https://doi.org/10.1111/1440-1681.13225

    Article  CAS  PubMed  Google Scholar 

  122. Shukla S, Fu P, Gupta S. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer. Apoptosis. 2014;19(5):883-894. doi: https://doi.org/10.1007/s10495-014-0971-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Shukla Y, Arora A, Taneja P. Antimutagenic potential of curcumin on chromosomal aberrations in Wistar rats. Mutat. Res. 2002;515(1-2):197-202. doi: https://doi.org/10.1016/s1383-5718(02)00016-5

    Article  CAS  PubMed  Google Scholar 

  124. Siddique YH, Afzal M. Antigenotoxic effect of apigenin against mitomycin C induced genotoxic damage in mice bone marrow cells. Food Chem. Toxicol. 2009;47(3):536-539. doi: https://doi.org/10.1016/j.fct.2008.12.006

    Article  CAS  PubMed  Google Scholar 

  125. Siddique YH, Beg T, Afzal M. Antigenotoxic effect of apigenin against anti-cancerous drugs. Toxicol. In Vitro. 2008;22(3):625-631. doi: https://doi.org/10.1016/j.tiv.2007.12.002

    Article  CAS  PubMed  Google Scholar 

  126. Singh BN, Rawat AK, Bhagat RM, Singh BR. Black tea: Phytochemicals, cancer chemoprevention, and clinical studies. Crit. Rev. Food Sci. Nutr. 2017;57(7):1394-1410. doi: https://doi.org/10.1080/10408398.2014.994700

    Article  CAS  PubMed  Google Scholar 

  127. Srivastava J.K, Gupta S. Antiproliferative and apoptotic effects of chamomile extract in various human cancer cells. J. Agric. Food Chem. 2007;55(23):9470-9478. doi: https://doi.org/10.1021/jf071953k

    Article  CAS  PubMed  Google Scholar 

  128. Sudheer AR, Muthukumaran S, Devipriya N, Devaraj H, Menon VP. Influence of ferulic acid on nicotine-induced lipid peroxidation, DNA damage and inflammation in experimental rats as compared to N-acetylcysteine. Toxicology. 2008;243(3):317-329. doi: https://doi.org/10.1016/j.tox.2007.10.016

    Article  CAS  PubMed  Google Scholar 

  129. Sudheer AR, Muthukumaran S, Kalpana C, Srinivasan M, Menon VP. Protective effect of ferulic acid on nicotine-induced DNA damage and cellular changes in cultured rat peripheral blood lymphocytes: a comparison with N-acetylcysteine. Toxicol. In Vitro. 2007;21(4):576-585. doi: https://doi.org/10.1016/j.tiv.2006.11.006

    Article  CAS  PubMed  Google Scholar 

  130. Thiyagarajan P, Kavitha K, Thautam A, Dixit M, Nagini S. Dietary chlorophyllin abrogates TGFβ signaling to modulate the hallmark capabilities of cancer in an animal model of forestomach carcinogenesis. Tumour Biol. 2014;35(7):6725-6737. doi: https://doi.org/10.1007/s13277-014-1849-5

    Article  CAS  PubMed  Google Scholar 

  131. Thiyagarajan P, Senthil Murugan R, Kavitha K, Anitha P, Prathiba D, Nagini S. Dietary chlorophyllin inhibits the canonical NF-κB signaling pathway and induces intrinsic apoptosis in a hamster model of oral oncogenesis. Food Chem. Toxicol. 2012;50(3-4):867-876. doi: https://doi.org/10.1016/j.fct.2011.12.019

    Article  CAS  PubMed  Google Scholar 

  132. Tian Y, Leung W, Yue K, Mak N. Cell death induced by MPPa-PDT in prostate carcinoma in vitro and in vivo. Biochem. Biophys. Res. Commun. 2006;348(2):413-420. doi: https://doi.org/10.1016/j.bbrc.2006.07.071

    Article  CAS  PubMed  Google Scholar 

  133. Walczak K, Marciniak S, Rajtar G. Cancer chemoprevention — selected molecular mechanisms. Postepy Hig. Med. Dosw. (Online). 2017;71:149-161. doi: 10.5604/ 01.3001.0010.3799

  134. Wang H, Xu YS, Wang ML, Cheng C, Bian R, Yuan H, Wang Y, Guo T, Zhu LL, Zhou H. Protective effect of naringin against the LPS-induced apoptosis of PC12 cells: Implications for the treatment of neurodegenerative disorders. Int. J. Mol. Med. 2017;39(4):819-830. doi: https://doi.org/10.3892/ijmm.2017.2904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wang IK, Lin-Shiau SY, Lin JK. Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur. J. Cancer. 1999;35(10):1517-1525.

    Article  CAS  Google Scholar 

  136. Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J. Exp. Clin. Cancer Res. 2011;30(1):87. doi: https://doi.org/10.1186/1756-9966-30-87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Wu MS, Lien GS, Shen SC, Yang LY, Chen YC. N-acetyl-Lcysteine enhances fisetin-induced cytotoxicity via induction of ROS-independent apoptosis in human colonic cancer cells. Mol. Carcinog. 2014;53, Suppl 1):E119-E129. doi: 10.1002/mc.22053

  138. Xie D, Yuan P, Wang D, Jin H, Chen H. Effects of naringin on the expression of miR-19b and cell apoptosis in human hepatocellular carcinoma. Oncol. Lett. 2017;14(2):1455-1459. doi: https://doi.org/10.3892/ol.2017.6278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Xu DP, Li Y, Meng X, Zhou T, Zhou Y, Zheng J, Zhang JJ, Li HB. Natural Antioxidants in Foods and Medicinal Plants: Extraction, Assessment and Resources. Int. J. Mol. Sci. 2017;18(1):96. doi: https://doi.org/10.3390/ijms18010096

    Article  CAS  PubMed Central  Google Scholar 

  140. Yamaoka M, Yamaguchi S, Suzuki T, Okuyama M, Nitobe J, Nakamura N, Mitsui Y, Tomoike H. Apoptosis in rat cardiac myocytes induced by Fas ligand: priming for Fasmediated apoptosis with doxorubicin. J. Mol. Cell Cardiol. 2000;32(6):881-889. doi: https://doi.org/10.1006/jmcc.2000.1132

    Article  CAS  PubMed  Google Scholar 

  141. Yan C, Kong D, Ge D, Zhang Y, Zhang X, Su C, Cao X. Mitomycin C induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via a mitochondrial-mediated pathway. Cell. Physiol. Biochem. 2015;35(3):1125-1136. doi: https://doi.org/10.1159/000373938

    Article  CAS  PubMed  Google Scholar 

  142. Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell. Biosci. 2017;7:50. doi: https://doi.org/10.1186/s13578-017-0179-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Yang J, Su Y, Richmond A. Antioxidants tiron and N-acetyl-L-cysteine differentially mediate apoptosis in melanoma cells via a reactive oxygen species-independent NF-kappaB pathway. Free Radic. Biol. Med. 2007;42(9):1369-1380. doi: https://doi.org/10.1016/j.freeradbiomed.2007.01.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Yedjou CG, Tchounwou CK, Haile S, Edwards F, Tchounwou PB. N-acetyl-cysteine protects against DNA damage associated with lead toxicity in HepG2 cells. Ethn. Dis. 2010;20(1, Suppl 1):S1-101-3.

  145. Yi YS. Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses. Mol. Nutr. Food Res. 2018;62(13):e1800147. doi: https://doi.org/10.1002/mnfr.201800147

    Article  CAS  PubMed  Google Scholar 

  146. Yilmaz D, Aydemir NC, Vatan O, Tüzün E, Bilaloglu R. Influence of naringin on cadmium-induced genomic damage in human lymphocytes in vitro. Toxicol. Ind. Health. 2012;28(2):114-121. doi: https://doi.org/10.1177/0748233711407241

    Article  CAS  PubMed  Google Scholar 

  147. Yilmaz D, Teksoy O, Bilaloglu R, Çinkilic N. Anti-genotoxic effect of naringin against bleomycin-induced genomic damage in human lymphocytes in vitro. Drug Chem. Toxicol. 2016;39(2):119-123. doi: https://doi.org/10.3109/01480545.2015.1039647

    Article  CAS  PubMed  Google Scholar 

  148. Yuan CH, Horng CT, Lee CF, Chiang NN, Tsai FJ, Lu CC, Chiang JH, Hsu YM, Yang JS, Chen FA. Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling. Environ. Toxicol. 2017;32(3):845-855. doi: https://doi.org/10.1002/tox.22284

    Article  CAS  PubMed  Google Scholar 

  149. Yun CH, Jeong HG, Jhoun JW, Guengerich FP. Non-specific inhibition of cytochrome P450 activities by chlorophyllin in human and rat liver microsomes. Carcinogenesis. 1995;16(6):1437-1440. doi: https://doi.org/10.1093/carcin/16.6.1437

    Article  CAS  PubMed  Google Scholar 

  150. Zeng L, Zhen Y, Chen Y, Zou L, Zhang Y, Hu F, Feng J, Shen J, Wei B. Naringin inhibits growth and induces apoptosis by a mechanism dependent on reduced activation of NF-κB/ COX-2-caspase-1 pathway in HeLa cervical cancer cells. Int. J. Oncol. 2014;45(5):1929-1936. doi: https://doi.org/10.3892/ijo.2014.2617

    Article  CAS  PubMed  Google Scholar 

  151. Zhang Z, Wang C, Lin J, Jin H, Wang K, Yan Y, Wang J, Wu C, Nisar M, Tian N, Wang X, Zhang X. Therapeutic potential of naringin for intervertebral disc degeneration: involvement of autophagy against oxidative stress-induced apoptosis in nucleus pulposus cells. Am. J. Chin. Med. 2018:1-20. doi: https://doi.org/10.1142/S0192415X18500805

  152. Zhao G, Han X, Cheng W, Ni J, Zhang Y, Lin J, Song Z. Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells. Oncol. Rep. 2017;37(4):2277-2285. doi: https://doi.org/10.3892/or.2017.5450

    Article  CAS  PubMed  Google Scholar 

  153. Zheng J, Lou JR, Zhang XX, Benbrook DM, Hanigan MH, Lind SE, Ding W.Q. N-Acetylcysteine interacts with copper to generate hydrogen peroxide and selectively induce cancer cell death. Cancer Lett. 2010;298(2):186-194. doi: https://doi.org/10.1016/j.canlet.2010.07.003

    Article  CAS  PubMed  Google Scholar 

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 171, No. 1, pp. 4-22, January, 2021

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Eremina, N.V., Zhanataev, A.K. & Durnev, A.D. Induced Cell Death as a Possible Pathway of Antimutagenic Action. Bull Exp Biol Med 171, 1–14 (2021). https://doi.org/10.1007/s10517-021-05161-z

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