Abstract
Vincristine-induced peripheral neuropathy (VIPN) is the main side effect and major reason for neuropathic pain in cancer survivors treated with vincristine. Vincristine, a chemotherapeutic antimitotic drug, is used frequently in combination chemotherapy. The primary purpose of the current study was to assess the protective effect of sodium selenite (SSe) on VIPN in vitro. Cytotoxicity effects of vincristine were evaluated using PC12 cells as a neuronal model. The cell culture studies were conducted in three groups based on the various treatments, including vincristine, SSe, and co-exposure to both compositions. Cell viability and cell cycle analyses were performed using MTT assay and flow cytometry, respectively. The level of mRNA expression of Bax and Bcl-2 was determined using qRT-PCR. According to the results, vincristine decreased the survival rate of PC12 cells. After 24 and 48 h exposure to different concentrations of vincristine (0.1–20 μΜ), the survival rate of PC12 cells decreased as compared to the control group. The results showed that treatment with 5 μΜ of vincristine resulted in apoptosis of PC12 cells. Interestingly,co-incubation of these cells with SSe significantly reduced the cell damage induced by vincristine. Furthermore, vincristine induced the inhibition of the G2 phase in PC 12 cells, and using SSe in combination with vincristine eliminated the inhibition of the cell cycle in the G2 phase. Briefly, our in vitro preliminary study showed that SSe might protect PC12 cells from vincristine-induced peripheral neuropathy during chemotherapy.
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References
Argyriou AA, Polychronopoulos P, Koutras A, Iconomou G, Gourzis P, Assimakopoulos K et al (2006) Is advanced age associated with increased incidence and severity of chemotherapy-induced peripheral neuropathy? Support Care Cancer 14:223–229
Beck J, Ferrucci L, Sun K, Walston J, Fried LP, Varadhan R et al (2007) Low serum selenium concentrations are associated with poor grip strength among older women living in the community. BioFactors 29:37–44
Behne D, Hilmert H, Scheid S, Gessner H, Elger W (1988) Evidence for specific selenium target tissues and new biologically important selenoproteins. Biochim Biophys Acta 966:12–21
Binte Hossain KF, Rahman MM, Sikder MT, Saito T, Hosokawa T, Kurasaki M (2018) Inhibitory effects of selenium on cadmium-induced cytotoxicity in PC12 cells via regulating oxidative stress and apoptosis. Food Chem Toxicol 114:180–189
Bota M, Fischer-Fodor E, Bochiș O-V, Cenariu M, Popa G, Blag CL et al (2019) Combined effect of propranolol, vincristine and bevacizumab on HUVECs and BJ cells. Exp Ther Med 17:307–315
Boyette-Davis JA, Walters ET, Dougherty PM (2015) Mechanisms involved in the development of chemotherapy-induced neuropathy. Pain Manag 5:285–296
Cai X, Shen YL, Zhu Q, Jia PM, Yu Y, Zhou L et al (2000) Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia. Leukemia 14:262–270
Carozzi VA, Canta A, Chiorazzi A (2015) Chemotherapy-induced peripheral neuropathy: what do we know about mechanisms? Neurosci Lett 596:90–107
Chresta CM, Masters JR, Hickman JA (1996) Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high Bax:Bcl-2 ratio. Can Res 56:1834–1841
Courtemanche H, Magot A, Ollivier Y, Rialland F, Leclair-Visonneau L, Fayet G et al (2015) Vincristine-induced neuropathy: atypical electrophysiological patterns in children. Muscle Nerve 52:981–985
Cuddihy AR, Oonnell MJ (2003) Cell-cycle responses to DNA damage in G. Int Rev Cytol 222:99–140
Dumontet C, Jordan MA (2010) Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 9:790–803
Erbil G, Ozbal S, Sonmez U, Pekcetin C, Tugyan K, Bagriyanik A et al (2008) Neuroprotective effects of selenium and ginkgo biloba extract (EGb761) against ischemia and reperfusion injury in rat brain. Neurosciences (riyadh) 13:233–238
Ertilav K, Nazıroğlu M, Ataizi ZS, Yıldızhan K (2020) Melatonin and selenium suppress docetaxel-induced TRPV1 activation, neuropathic pain and oxidative neurotoxicity in mice. Biol Trace Element Res. 199:1469–1487
Gilchrist LS, Marais L, Tanner L (2014) Comparison of two chemotherapy-induced peripheral neuropathy measurement approaches in children. Support Care Cancer 22:359–366
Gomber S, Dewan P, Chhonker D (2010) Vincristine induced neurotoxicity in cancer patients. Indian J Pediatr 77:97–100
Gromer S, Eubel JK, Lee BL, Jacob J (2005) Human selenoproteins at a glance. Cell Mol Life Sci 62:2414–2437
Hausheer FH, Schilsky RL, Bain S, Berghorn EJ, Lieberman F (2006) Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol 33:15–49
Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G et al (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:1941–1967
Hwang DY, Cho JS, Oh JH, Shim SB, Jee SW, Lee SH et al (2005) Differentially expressed genes in transgenic mice carrying human mutant presenilin-2 (N141I): correlation of selenoprotein M with Alzheimer’s disease. Neurochem Res 30:1009–1019
Johnson IS, Armstrong JG, Gorman M, Burnett JP Jr (1963) The vinca alkaloids: a new class of oncolytic agents. Can Res 23:1390–1427
Kandaş NO, Randolph C, Bosland MC (2009) Differential effects of selenium on benign and malignant prostate epithelial cells: stimulation of LNCaP cell growth by noncytotoxic, low selenite concentrations. Nutr Cancer 61:251–264
Kieliszek M, Blazejak S (2013) Selenium: significance, and outlook for supplementation. Nutrition 29:713–718
Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R et al (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443
Kung AL, Zetterberg A, Sherwood SW, Schimke RT (1990) Cytotoxic effects of cell cycle phase specific agents: result of cell cycle perturbation. Can Res 50:7307–7317
Lavoie Smith EM, Li L, Chiang C, Thomas K, Hutchinson RJ, Wells EM et al (2015) Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia. J Peripher Nerv Syst 20:37–46
Legha SS (1986) Vincristine neurotoxicity. Pathophysiol Manag Med Toxicol 1:421–427
Lemarie A, Morzadec C, Mérino D, Micheau O, Fardel O, Vernhet L (2006) Arsenic trioxide induces apoptosis of human monocytes during macrophagic differentiation through nuclear factor-kappaB-related survival pathway down-regulation. J Pharmacol Exp Ther 316:304–314
Lin CR, Cheng JT, Lin FC, Chou AK, Lee TC, Chen JT et al (2002) Effect of thiopental, propofol, and etomidate on vincristine toxicity in PC12 cells. Cell Biol Toxicol 18:63–70
Lobert S, Vulevic B, Correia JJ (1996) Interaction of vinca alkaloids with tubulin: a comparison of vinblastine, vincristine, and vinorelbine. Biochemistry 35:6806–6814
Loef M, Schrauzer GN, Walach H (2011) Selenium and Alzheimer’s disease: a systematic review. J Alzheimers Dis 26:81–104
Milcan A, Arslan E, Bagdatoglu OT, Bagdatoglu C, Polat G, Kanik A et al (2004) The effect of alprostadil on ischemia-reperfusion injury of peripheral nerve in rats. Pharmacol Res 49:67–72
Mora E, Smith EML, Donohoe C, Hertz DL (2016) Vincristine-induced peripheral neuropathy in pediatric cancer patients. Am J Cancer Res 6:2416–2430
Nakayama A, Hill KE, Austin LM, Motley AK, Burk RF (2007) All regions of mouse brain are dependent on selenoprotein P for maintenance of selenium. J Nutr 137:690–693
Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H et al (1998) Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci USA 95:14681–14686
Ola MS, Nawaz M, Ahsan H (2011) Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 351:41–58
Rahman MM, Uson-Lopez RA, Sikder MT, Tan G, Hosokawa T, Saito T et al (2018) Ameliorative effects of selenium on arsenic-induced cytotoxicity in PC12 cells via modulating autophagy/apoptosis. Chemosphere 196:453–466
Ramchandren S, Leonard M, Mody RJ, Donohue JE, Moyer J, Hutchinson R et al (2009) Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia. J Peripher Nerv Syst 14:184–189
Sawaguchi Y, Ueno S, Nishiyma Y, Yamazaki R, Matsuzaki T (2015) Establishment of a novel in vitro model for predicting incidence and severity of microtubule-targeting agent-induced peripheral neuropathy. Anticancer Res 35:6431–6437
Silva A, Wang Q, Wang M, Ravula SK, Glass JD (2006) Evidence for direct axonal toxicity in vincristine neuropathy. J Peripher Nerv Syst 11:211–216
Silverman JA, Deitcher SR (2013) Marqibo(R) (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother Pharmacol 71:555–564
Souza PS, Vasconcelos FC, De Souza Reis FR, Nestal De Moraes G, Maia RC (2011) P-glycoprotein and survivin simultaneously regulate vincristine-induced apoptosis in chronic myeloid leukemia cells. Int J Oncol 39:925–933
Starobova H, Vetter I (2017) Pathophysiology of chemotherapy-induced peripheral neuropathy. Front Mol Neurosci 10:174
Steinbrenner H, Sies H (2013) Selenium homeostasis and antioxidant selenoproteins in brain: implications for disorders in the central nervous system. Arch Biochem Biophys 536:152–157
Tapiero H, Townsend DM, Tew KD (2003) The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother = Biomedecine & Pharmacotherapie. 57:134–144
Tu Y, Cheng S, Zhang S, Sun H, Xu Z (2013) Vincristine induces cell cycle arrest and apoptosis in SH-SY5Y human neuroblastoma cells. Int J Mol Med 31:113–119
Wang X, Huan Y, Li C, Cao H, Sun S, Lei L et al (2020) Diphenyl diselenide alleviates diabetic peripheral neuropathy in rats with streptozotocin-induced diabetes by modulating oxidative stress. Biochem Pharmacol 182:114221
Yu Y, Ma X, Yang T, Li B, Xie K, Liu D et al (2015) Protective effect of hydrogen-rich medium against high glucose-induced apoptosis of Schwann cells in vitro. Mol Med Rep 12:3986–3992
Zajączkowska R, Kocot-Kępska M, Leppert W, Wrzosek A, Mika J, Wordliczek J (2019) Mechanisms of chemotherapy-induced peripheral neuropathy. Int J Mol Sci 20:1451
Zhu L, Han MB, Gao Y, Wang H, Dai L, Wen Y et al (2015) Curcumin triggers apoptosis via upregulation of Bax/Bcl-2 ratio and caspase activation in SW872 human adipocytes. Mol Med Rep 12:1151–1156
Zhu L, Hao J, Cheng M, Zhang C, Huo C, Liu Y et al (2018) Hyperglycemia-induced Bcl-2/Bax-mediated apoptosis of Schwann cells via mTORC1/S6K1 inhibition in diabetic peripheral neuropathy. Exp Cell Res 367:186–195
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The authors acknowledge Iran University of Medical Sciences Research and Technology support.
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This study was funded by Iran University of Medical Sciences.
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Conception and design of the study: DJ and SSE, Acquisition of data: SSE and DJ, Analysis and/or interpretation: SSE, DJ, SM, Drafting the manuscript: SM, DJ, SSE, Revising the manuscript critically for important intellectual content: PT, DJ and SM. Artwork preparation: DJ.
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Jafari, D., Eslami, S.S., Malih, S. et al. Protective effect of selenium on vincristine-induced peripheral neuropathy in PC12 cell line. Cytotechnology 74, 539–547 (2022). https://doi.org/10.1007/s10616-022-00543-1
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DOI: https://doi.org/10.1007/s10616-022-00543-1