Volume 32, Issue 7 (October 2021)                   Studies in Medical Sciences 2021, 32(7): 525-536 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

URL: http://umj.umsu.ac.ir/article-1-5589-en.html
Assistant Professor, Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran (Corresponding Author , mortazabagheri@yahoo.com
Abstract:   (1626 Views)
Background & Aims: Ovarian cancer is the seventh most common cancer and the fifth most common cause of death among women worldwide. Therefore, it is necessary to find new drugs that increase the effectiveness of chemotherapy drugs and the possibility of using them in lower doses, which leads to a reduction in side effects. The aim of this study was to evaluate the effect of melatonin on the expression of XIAP, Survivin, AKT, and caspase 3 genes in order to increase cisplatin sensitivity in cultured OVCAR3 cells.
Materials & Methods: In this study, OVCAR3 cells with different concentrations of melatonin (0.001, 0.312, 0.625, 1.25, 2.5, 5,10 μM) and different concentrations of cisplatin (0.001, 0.937, 1.875, 3.75, 7.5, 15 μM) were cultivated at 24, 48, and 72 hours. Then, cytotoxicity was assessed by MTT assay. Real-time PCR test was performed to evaluate the relative gene expression level of XIAP, Survivin, AKT, and caspase 3 genes in control, melatonin, cisplatin, and a combination of melatonin and cisplatin groups.
Results: The results of this study showed that melatonin inhibits the proliferation of cultured OVCAR3 cells based on a dose and time-dependent mechanism. The results of analysis showed that there is a significant increase in the gene expression level of caspase 3 regarding melatonin and melatonin-cisplatin groups. Also, the expression of Survivin apoptosis inhibitor gene in melatonin-cisplatin combination group decreased (borderline difference). There were no significant changes in tested groups regarding relative gene expression of Xiap and Akt.
Conclusion: The findings of this study show that OVCAR3 cells became more sensitive to cisplatin in the presence of melatonin. It can be used to manage patients with ovarian cancer.
Full-Text [PDF 704 kb]   (434 Downloads)    
Type of Study: Research | Subject: General

1. Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol 2009; 20(3): 556 -63. [DOI:10.1093/annonc/mdn642] [PMID]
2. Arab M, Khayamzadeh M, Tehranian A, Tabatabaeefar M, Hosseini M, Anbiaee R, et al. Incidence rate of ovarian cancer in Iran in comparison with developed countries. Indian J Cancer 2010; 47(3): 322-7. [DOI:10.4103/0019-509X.64721] [PMID]
3. Lalwani N, Prasad SR, Vikram R, Shanbhogue AK, Huettner PC, Fasih N. Histologic, molecular, and cytogenetic features of ovarian cancers: implications for diagnosis and treatment. Radiographics 2011; 31(3):625-46. [DOI:10.1148/rg.313105066] [PMID]
4. Tortolero-Luna G, Mitchell MF. Epidemiology of ovarian cancer. J Cell Biochem Suppl 1995; 23: 200-7. [DOI:10.1002/jcb.240590927] [PMID]
5. Kim HJ, Oh GS, Lee JH, Lyu AR, Ji HM, Lee SH, et al. Cisplatin ototoxicity involves cytokines and STAT6 signaling network. Cell Res 2011; 21(6): 944-56. [DOI:10.1038/cr.2011.27] [PMID] [PMCID]
6. Mueller S, Schittenhelm M, Honecker F, Malenke E, Lauber K, Wesselborg S, et al. Cell-cycle progression and response of germ cell tumors to cisplatin in vitro. Int J Oncol 2006; 29(2): 471-9. [DOI:10.3892/ijo.29.2.471] [PMID]
7. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014; 740: 364-78. [DOI:10.1016/j.ejphar.2014.07.025] [PMID] [PMCID]
8. Maiti AK. Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells. Pharmacogenomics J 2010; 10(2):94-104. [DOI:10.1038/tpj.2009.49] [PMID]
9. Ayyagari VN, Hsieh TH, Diaz-Sylvester PL, Brard L. Evaluation of the cytotoxicity of the Bithionol-cisplatin combination in a panel of human ovarian cancer cell lines. BMC cancer 2017; 17(1): 1-5. [DOI:10.1186/s12885-016-3034-2] [PMID] [PMCID]
10. Lambert HE, Gregory WM, Nelstrop AE, Rustin GJ. Long-term survival in 463 women treated with platinum analogs for advanced epithelial carcinoma of the ovary: life expectancy compared to women of an age-matched normal population. Int J Gynecol Cancer 2004; 14(5): 772-8. https://doi.org/10.1111/j.1048-891X.2004.014507.x [DOI:10.1136/ijgc-00009577-200409000-00006] [PMID]
11. Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 1991; 12(2):151-80. [DOI:10.1210/edrv-12-2-151] [PMID]
12. Fan LL, Sun GP, Wei W, Wang ZG, Ge L, Fu WZ, et al. Melatonin and doxorubicin synergistically induce cell apoptosis in human hepatoma cell lines. World J Gastroenterol 2010; 16(12):1473-81. [DOI:10.3748/wjg.v16.i12.1473] [PMID] [PMCID]
13. Altun A, Ugur-Altun B. Melatonin: Therapeutic and clinical utilization. Int J Clin Pract 2007; 61(5): 835-45. [DOI:10.1111/j.1742-1241.2006.01191.x] [PMID]
14. Bojková B, Kubatka P, Qaradakhi T, Zulli A, Kajo K. Melatonin May Increase Anticancer Potential of Pleiotropic Drugs. Int J Mol Sci 2018; 19(12):3910. [DOI:10.3390/ijms19123910] [PMID] [PMCID]
15. Hill SM, Frasch T, Xiang S, Yuan L, Duplessis T, Mao L. Basic mechanisms involved in the anti-cancer effects of melatonin. Curr Med Chem 2010; 36: 4462-81. [Google Scholar]
16. Su Z, Yang Z, Xu Y, Chen Y, Yu Q. Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer 2015; 14(1): 48. [DOI:10.1186/s12943-015-0321-5] [PMID] [PMCID]
17. Troy CM, Jean YY. Caspases: therapeutic targets in neurologic disease. Neurotherapeutics 2015; 12: 42-8. [DOI:10.1007/s13311-014-0307-9] [PMID] [PMCID]
18. Brady SW, Zhang J, Tsai MH, Yu D. PI3K-independent mTOR activation pro-Motes lapatinib resistance and IAP expression that can be effectively reversed by mTOR and Hsp90 inhibition. Cancer Biol Ther 2015; 16: 402-11. [DOI:10.1080/15384047.2014.1002693] [PMID] [PMCID]
19. Rodriguez C, Martín V, Herrera F, García-Santos G, Rodriguez-Blanco J, Casado-Zapico S, et al. Mechanisms involved in the pro-apoptotic effect of melatonin in cancer cells. Int J Mol Sci 2013; 14(4):6597-613. [DOI:10.3390/ijms14046597] [PMID] [PMCID]
20. Carpentieri A, De Barboza GD, Areco V, López MP, De Talamoni NT. New perspectives in melatonin uses. Pharmacol Res 2012; 65(4):437-44. [DOI:10.1016/j.phrs.2012.01.003] [PMID]
21. Pariente R, Pariente JA, Rodríguez AB, Espino J. Melatonin sensitizes human cervical cancer HeLa cells to cisplatin-induced cytotoxicity and apoptosis: effects on oxidative stress and DNA fragmentation. J Pineal Res 2016; 60(1):55-64 [DOI:10.1111/jpi.12288] [PMID]
22. Blask DE, Sauer LA, Dauchy RT. Melatonin as a chronobiotic/anticancer agent: cellular, biochemical, and molecular mechanisms of action and their implications for circadian-based cancer therapy. Curr Top Med Chem 2002; 2(2):113-32. [DOI:10.2174/1568026023394407] [PMID]
23. Susan Elmore. Apoptosis: A Review of Programmed Cell Death. Toxicol Pathol 2007; 35(4): 495-516. [DOI:10.1080/01926230701320337] [PMID] [PMCID]
24. Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 2011; 30: 87. [DOI:10.1186/1756-9966-30-87] [PMID] [PMCID]
25. Hunter AM, LaCasse EC, Korneluk RG. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis 2007; 12: 1543-68. [DOI:10.1007/s10495-007-0087-3] [PMID]
26. Jaiswal PK, Goel A, Goel A. Survivin: A molecular biomarker in cancer. Indian J Med Res 2015; 141(4): 389-97. [DOI:10.4103/0971-5916.159250] [PMID] [PMCID]
27. Fan L, Sun G, Ma T, Zhong F, Wei W. Melatonin overcomes apoptosis resistance in human hepatocellular carcinoma by targeting surviving and XIAP. J Pineal Res 2013; 55(2):174-83. [DOI:10.1111/jpi.12060] [PMID]
28. Hunter AM, LaCasse EC, Korneluk RG. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis 2007; 12: 1543-68. [DOI:10.1007/s10495-007-0087-3] [PMID]
29. Danson S, Dean E, Dive C, Ranson M. IAPs as a target for anticancer therapy. Curr Cancer Drug Targets 2007; 7:785-94. [DOI:10.2174/156800907783220471] [PMID]
30. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer. Nat Rev Drug Discov 2009; 8(8): 627-44. [DOI:10.1038/nrd2926] [PMID] [PMCID]
31. Amornphimoltham P, Patel V, Sodhi A, Nikitakis NG, Sauk JJ, Sausville EA, et al. Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck. Cancer Res 2005; 65(21):9953-61. [DOI:10.1158/0008-5472.CAN-05-0921] [PMID]
32. Brazil DP, Yang ZZ, Hemmings BA Advances in protein kinase B urviving: AKTion on multiple fronts. Trends Biochem Sci 2004; 29: 233-42. [DOI:10.1016/j.tibs.2004.03.006] [PMID]
33. Proietti S, Cucina A, D'Anselmi F, Dinicola S, Pasqualato A, Lisi E, et al. Melatonin and vitamin D3 synergistically down-regulate Akt and MDM2 leading to TGFbeta-1-dependent growth inhibition of breast cancer cells. J Pineal Res 2011; 50(2):150-8. [DOI:10.1111/j.1600-079X.2010.00824.x] [PMID]
34. Asselin E, Mills GB, Tsang BK.XIAP regulates Akt activity and caspase-3-dependent cleavage during cisplatin-induced apoptosis in human ovarian epithelial cancer cells. Cancer Res 2001; 61(5):1862-8. [Google Scholar]
35. Gagnon V, Van Themsche C, Turner S, Leblanc V, Asselin E. Akt and XIAP regulate the sensitivity of human uterine cancer cells to cisplatin, doxorubicin and taxol. Apoptosis 2008; 13:259-71. [DOI:10.1007/s10495-007-0165-6] [PMID]
36. Jiang C, Yi XP, Shen H, Li YX. Targeting X-linked inhibitor of apoptosis protein inhibits pancreatic cancer cell growth through p-Akt depletion. World J Gastroenterol 2012; 18(23):2956-65. [DOI:10.3748/wjg.v18.i23.2956] [PMID] [PMCID]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2023 CC BY-NC 4.0 | Studies in Medical Sciences

Designed & Developed by : Yektaweb