The promising oncostatic effects of melatonin against ovarian cancer

Melatonin and ovarian cancer

  • Naba Kumar Das Department Physiology, Midnapore College, Midnapore, Paschim Medinipur, West Bengal, India, 721101
  • Saptadip Samanta Department Physiology, Midnapore College, Midnapore, Paschim Medinipur, West Bengal, India, 721101


Melatonin is a pineal hormone, secreted at the subjective night. It is involved in the regulation of many physiological functions, including the sleep-wake cycle, gonadal activity, free radical scavenging, immunomodulation, neuro-protection, and cancer progression. Melatonin acts through cell surface receptors (MT1 and MT2) as well as nuclear receptors. Circadian dysfunction can alter the secretion of melatonin. Inappropriate melatonin level promotes the initiation of many pathologies including cancer. Ovarian cancer is a common form of gynecological disease. Several studies indicate the profound link between impaired melatonin secretion and the progression of ovarian cancer. Melatonin exerts oncostatic effects in multiple ways; it acts as a potent antioxidant, induces apoptosis, and regulates metabolism, and chronic inflammatory response in ovarian cancer cells. Moreover, melatonin improves the efficacy of the current treatment regimen of ovarian cancer and can be used as an adjuvant.

Keywords: melatonin, ovarian cancer, apoptosis, inflammatory response, chemotherapy


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1. Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, Fougerou C. Melatonin: pharmacology, functions and therapeutic benefits. Current neuropharmacology. 2017; 15(3):434-443.
2. Nogueira LM, Sampson JN, Chu LW, Yu K, Andriole G, Church T, Stanczyk FZ, Koshiol J, Hsing AW. Individual variations in serum melatonin levels through time: implications for epidemiologic studies. PLoS one. 2013 8(12):e83208.
3. Zare H, Shafabakhsh R, Reiter RJ, Asemi Z. Melatonin is a potential inhibitor of ovarian cancer: molecular aspects. Journal of ovarian research. 2019; 12(1):1-8.
4. Buijs RM, Scheer FA, Kreier F, Yi C, Bos N, Goncharuk VD, Kalsbeek A. Organization of circadian functions: interaction with the body. Progress in brain research. 2006; 153:341-360.
5. Androulakis IP. Circadian rhythms and the HPA axis: A systems view. WIREs Mechanisms of Disease. 2021; 13(4):e1518.
6. Poole EM, Schernhammer E, Mills L, Hankinson SE, Tworoger SS. Urinary melatonin and risk of ovarian cancer. Cancer Causes & Control. 2015; 26(10):1501-1516.
7. Talib WH. Melatonin and cancer hallmarks. Molecules. 2018; 23(3):518.
8. Samanta S. Physiological and pharmacological perspectives of melatonin, Arch Physiol Biochem. 2020a.
9. Chen J. The cell-cycle arrest and apoptotic functions of p53 in tumour initiation and progression. Cold Spring Harbor perspectives in medicine. 2016; 6(3):a026104.
10. Chuffa LG, Fioruci-Fontanelli BA, Mendes LO, Fávaro WJ, Pinheiro PF, Martinez M, Martinez FE. Characterization of chemically induced ovarian carcinomas in an ethanol-preferring rat model: influence of long-term melatonin treatment. PloS one. 2013; 8(12):e81676.
11. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2018; 68(6):394-424.
12. Ostrin LA. Ocular and systemic melatonin and the influence of light exposure. Clinical and experimental optometry. 2019; 102(2):99-108.
13. Cohen M, Lippman M, Chabner B. Role of pineal gland in aetiology and treatment of breast cancer. The Lancet. 1978 14; 312(8094):814-816.
14. Voordouw BC, Euser R, Verdonk RE, Alberda BT, de Jong FH, Drogendijk AC, Fauser BC, Cohen M. Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. The Journal of Clinical Endocrinology & Metabolism. 1992; 74(1):108-117.
15. Stocker LJ, Macklon NS, Cheong YC, Bewley SJ. Influence of shift work on early reproductive outcomes: a systematic review and meta-analysis. Obstetrics & Gynecology. 2014; 124(1):99-110.
16. Vijayalaxmi, Thomas Jr CR, Reiter RJ, Herman TS. Melatonin: from basic research to cancer treatment clinics. Journal of Clinical Oncology. 2002; 20(10):2575-2601.
17. Favero G, Moretti E, Bonomini F, Reiter RJ, Rodella LF, Rezzani R. Promising antineoplastic actions of melatonin. Frontiers in pharmacology. 2018; 9:1086.
18. Huang CY, Cheng M, Lee NR, Huang HY, Lee WL, Chang WH, Wang PH. Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer. International journal of environmental research and public health. 2020; 17(7):2213.
19. Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nature Reviews Disease Primers. 2016; 2(1):1-22.
20. Nero C, Ciccarone F, Pietragalla A, Duranti S, Daniele G, Salutari V, Carbone MV, Scambia G, Lorusso D. Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors. Cancers. 2021; 13(6):1298.
21. Sato S, Itamochi H. Neoadjuvant chemotherapy in advanced ovarian cancer: latest results and place in therapy. Therapeutic advances in medical oncology. 2014; 6(6):293-304.
22. Yang WL, Lu Z, Bast Jr RC. The role of biomarkers in the management of epithelial ovarian cancer. Expert review of molecular diagnostics. 2017; 17(6):577-591.
23. Fathalla MF. Incessant ovulation—a factor in ovarian neoplasia. Lancet. 1971; 2(7716):163.
24. Cramer DW, Welch WR. Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis. Journal of the National Cancer Institute. 1983; 71(4):717-721.
25. Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. Journal of the National Cancer Institute. 1998; 90(23):1774-1786.
26. Boots CE, Jungheim ES. Inflammation and human ovarian follicular dynamics. InSeminars in reproductive medicine. NIH Public Access, 2015; 33(4):270-275.
27. Macciò A & Madeddu C. Inflammation and ovarian cancer. Cytokine. 2012; 58(2):133-147.
28. Cardenas C, Alvero AB, Yun BS, Mor G. Redefining the origin and evolution of ovarian cancer: a hormonal connection. Endocrine-related cancer. 2016; 23(9):R411-R422.
29. Fathalla MF. Incessant ovulation and ovarian cancer–a hypothesis re-visited. Facts, views & vision in ObGyn. 2013; 5(4):292-297.
30. Xu J, Zheng T, Hong W, Ye H, Hu C, Zheng Y. Mechanism for the decision of ovarian surface epithelial stem cells to undergo neo-oogenesis or ovarian tumorigenesis. Cellular Physiology and Biochemistry. 2018; 50(1):214-232.
31. Enninga EA, Holtan SG, Creedon DJ, Dronca RS, Nevala WK, Ognjanovic S, Markovic SN. Immunomodulatory effects of sex hormones: requirements for pregnancy and relevance in melanoma. InMayo Clinic Proceedings, 2014; 89(4): 520-535.
32. Gharwan H, Bunch KP, Annunziata CM. The role of reproductive hormones in epithelial ovarian carcinogenesis. Endocrine-related cancer. 2015; 22(6):R339-R363.
33. Chesang JJ. Pathogenesis of ovarian cancer: current perspectives. East African Medical Journal. 2017; 94(7):561-574.
34. Bhatti P, Cushing-Haugen KL, Wicklund KG, Doherty JA, Rossing MA. Nightshift work and risk of ovarian cancer. Occupational and environmental medicine. 2013; 70(4):231-237.
35. Carter BD, Diver WR, Hildebrand JS, Patel AV, Gapstur SM. Circadian disruption and fatal ovarian cancer. American journal of preventive medicine. 2014; 46(3):S34-S41.
36. Liu L, Zhang S, Bao J, He X, Tong D, Chen C, Ying Q, Zhang Q, Zhang C, Li J. Melatonin improves laying performance by enhancing intestinal amino acids transport in hens. Frontiers in endocrinology. 2018; 9:426.
37. Shen CJ, Chang CC, Chen YT, Lai CS, Hsu YC. Melatonin suppresses the growth of ovarian cancer cell lines (OVCAR-429 and PA-1) and potentiates the effect of G1 arrest by targeting CDKs. International journal of molecular sciences. 2016 ;17(2):176
38. Zemła A, Grzegorek I, Dzięgiel P, Jabłońska K. Melatonin synergizes the chemotherapeutic effect of cisplatin in ovarian cancer cells independently of MT1 melatonin receptors. in vivo. 2017; 31(5):801-809.
39. Akbarzadeh M, Movassaghpour AA, Ghanbari H, Kheirandish M, Maroufi NF, Rahbarghazi R, Nouri M, Samadi N. The potential therapeutic effect of melatonin on human ovarian cancer by inhibition of invasion and migration of cancer stem cells. Scientific reports. 2017; 7(1):1-1.
40. Lopes JR, Gelaleti GB, Moschetta MG, Sonehara NM, Hellmén E, Zanon C. F.; Oliani, SM; Zuccari, DA Effect of melatonin in epithelial mesenchymal transition markers and invasive properties of breast cancer stem cells of canine and human cell lines. PLoS One. 2016; 11(3):e0150407.
41. Walcher L, Kistenmacher AK, Suo H, Kitte R, Dluczek S, Strauß A, Blaudszun AR, Yevsa T, Fricke S, Kossatz-Boehlert U. Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Frontiers in Immunology. 2020; 11:1280.
42. Quintero-Fabián S, Arreola R, Becerril-Villanueva E, Torres-Romero JC, Arana-Argáez V, Lara-Riegos J, Ramírez-Camacho MA, Alvarez-Sánchez ME. Role of matrix metalloproteinases in angiogenesis and cancer. Frontiers in oncology. 2019; 9:1370.
43. Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nature communications. 2020; 11(1):1-9.
44. Cabral-Pacheco GA, Garza-Veloz I, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N, Martinez-Fierro ML. The roles of matrix metalloproteinases and their inhibitors in human diseases. International journal of molecular sciences. 2020; 21(24):9739.
45. Chuffa LG, Reiter RJ, Lupi LA. Melatonin as a promising agent to treat ovarian cancer: molecular mechanisms. Carcinogenesis. 2017; 38(10):945-952.
46. Talib WH, Alsayed AR, Abuawad A, Daoud S, Mahmod AI. Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities. Molecules. 2021; 26(9):2506.
47. Bojková B, Kubatka P, Qaradakhi T, Zulli A, Kajo K. Melatonin may increase anticancer potential of pleiotropic drugs. International journal of molecular sciences. 2018; 19(12):3910.
48. Mendonsa AM, Na TY, Gumbiner BM. E-cadherin in contact inhibition and cancer. Oncogene. 2018; 37(35):4769-4780.
49. Kaszak I, Witkowska-Piłaszewicz O, Niewiadomska Z, Dworecka-Kaszak B, Ngosa Toka F, Jurka P. Role of cadherins in cancer—a review. International Journal of Molecular Sciences. 2020; 21(20):7624.
50. Burandt E, Lübbersmeyer F, Gorbokon N, Büscheck F, Luebke AM, Menz A, Kluth M, Hube-Magg C, Hinsch A, Höflmayer D, Weidemann S. E-Cadherin expression in human tumors: a tissue microarray study on 10,851 tumors. Biomarker research. 2021; 9(1):1-7.
51. Anbalagan M, Rowan BG. Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer. Molecular and cellular endocrinology. 2015; 418:264-472.
52. Gurunathan S, Qasim M, Kang MH, Kim JH. Role and therapeutic potential of melatonin in various types of cancers. OncoTargets and therapy. 2021; 14:2019-2052.
53. Ling L, Alattar A, Tan Z, Shah FA, Ali T, Alshaman R, Koh PO, Li S. A potent antioxidant endogenous neurohormone melatonin, rescued MCAO by attenuating oxidative stress-associated neuroinflammation. Frontiers in Pharmacology. 2020; 11:1220.
54. Samanta S. Melatonin: an endogenous miraculous indolamine, fights against cancer progression. J Cancer Res Clin Oncol. 2020b;146:1893–1922.
55. Hasanuzzaman M, Bhuyan MH, Zulfiqar F, Raza A, Mohsin SM, Mahmud JA, Fujita M, Fotopoulos V. Reactive oxygen species and antioxidant defense in plants under abiotic stress: Revisiting the crucial role of a universal defense regulator. Antioxidants. 2020; 9(8):681.
56. Liu F, Ng TB. Effect of pineal indoles on activities of the antioxidant defense enzymes superoxide dismutase, catalase, and glutathione reductase, and levels of reduced and oxidized glutathione in rat tissues. Biochemistry and Cell Biology. 2000; 78(4):447-453.
57. Vázquez J, González B, Sempere V, Mas A, Torija MJ, Beltran G. Melatonin reduces oxidative stress damage induced by hydrogen peroxide in Saccharomyces cerevisiae. Frontiers in microbiology. 2017; 8:1066.
58. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria journal of medicine. 2018; 54(4):287-293.
59. Lopez A, Ortiz F, Doerrier C, Venegas C, Fernandez-Ortiz M, Aranda P, Diaz-Casado ME, Fernandez-Gil B, Barriocanal-Casado E, Escames G, Lopez LC. Mitochondrial impairment and melatonin protection in parkinsonian mice do not depend of inducible or neuronal nitric oxide synthases. PLoS One. 2017; 12(8):e0183090.
60. Karbownik M, Tan DX, Reiter RJ. Melatonin reduces the oxidation of nuclear DNA and membrane lipids induced by the carcinogen δ‐aminolevulinic acid. International journal of cancer. 2000; 88(1):7-11.
61. Pourhanifeh MH, Hosseinzadeh A, Dehdashtian E, Hemati K, Mehrzadi S. Melatonin: new insights on its therapeutic properties in diabetic complications. Diabetology & metabolic syndrome. 2020; 12(1):1-20.
62. Reiter RJ, Rosales-Corral SA, Manchester LC, Tan DX. Peripheral reproductive organ health and melatonin: ready for prime time. International journal of molecular sciences. 2013; 14(4):7231-7272.
63. Yeh CM, Su SC, Lin CW, Yang WE, Chien MH, Reiter RJ, Yang SF. Melatonin as a potential inhibitory agent in head and neck cancer. Oncotarget. 2017; 8(52):90545.
64. Sun TC, Liu XC, Yang SH, Song LL, Zhou SJ, Deng SL, Tian L, Cheng LY. Melatonin inhibits oxidative stress and apoptosis in cryopreserved ovarian tissues via Nrf2/HO-1 signalling pathway. Frontiers in Molecular Biosciences. 2020; 7.
65. Cutando A, Lopez-Valverde A, Arias-Santiago S, De Vicente J, DE DIEGO RG. Role of melatonin in cancer treatment. Anticancer research. 2012; 32(7):2747-2753.
66. Cordara G, van Eerde A, Grahn EM, Winter HC, Goldstein IJ, Krengel U. An unusual member of the papain superfamily: mapping the catalytic cleft of the Marasmius oreades agglutinin (MOA) with a caspase inhibitor. PloS one. 2016; 11(2):e0149407.
67. Capo-Chichi CD, Cai KQ, Xu XX. Overexpression and cytoplasmic localization of caspase-6 is associated with lamin A degradation in set of ovarian cancers. Biomarker research. 2018; 6(1):1-2.
68. Tsai CC, Lin YJ, Yu HR, Sheen JM, Tain YL, Huang LT, Tiao MM. Melatonin alleviates liver steatosis induced by prenatal dexamethasone exposure and postnatal high fat diet. Experimental and therapeutic medicine. 2018; 16(2):917-924.
69. Chuffa LG, Lupi Júnior LA, Seiva FR, Martinez M, Domeniconi RF, Pinheiro PF, Dos Santos LD, Martinez FE. Quantitative proteomic profiling reveals that diverse metabolic pathways are influenced by melatonin in an in vivo model of ovarian carcinoma. Journal of proteome research. 2016; 15(10):3872-3882.
70. Yang-Hartwich Y, Soteras MG, Lin ZP, Holmberg J, Sumi N, Craveiro V, Liang M, Romanoff E, Bingham J, Garofalo F, Alvero A. p53 protein aggregation promotes platinum resistance in ovarian cancer. Oncogene. 2015; 34(27):3605-3016.
71. Casado J, Iñigo-Chaves A, Jiménez-Ruiz SM, Ríos-Arrabal S, Carazo-Gallego Á, González-Puga C, Núñez MI, Ruíz-Extremera Á, Salmerón J, León J. AA-NAT, MT1 and MT2 correlates with cancer stem-like cell markers in colorectal cancer: study of the influence of stage and p53 status of tumours. International journal of molecular sciences. 2017; 18(6):1251.
72. Zhang L, Zhang Z, Wang F, Tian X, Ji P, Liu G. Effects of melatonin administration on embryo implantation and offspring growth in mice under different schedules of photoperiodic exposure. Reproductive Biology and Endocrinology. 2017; 15(1):1-9.
73. Pan LL, Wang AY, Huang YQ, Luo Y, Ling M. Mangiferin induces apoptosis by regulating Bcl-2 and Bax expression in the CNE2 nasopharyngeal carcinoma cell line. Asian Pacific Journal of Cancer Prevention. 2014; 15(17):7065-7068.
74. Menéndez-Menéndez J, Martínez-Campa C. Melatonin: an anti-tumor agent in hormone-dependent cancers. International journal of endocrinology. 2018; 2; 2018.
75. Mortezaee K, Najafi M, Farhood B, Ahmadi A, Potes Y, Shabeeb D, Musa AE. Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review. Life sciences. 2019; 228:228-2241.
76. Zhang X, Hou G, Liu A, Xu H, Guan Y, Wu Y, Deng J, Cao X. Matrine inhibits the development and progression of ovarian cancer by repressing cancer associated phosphorylation signalling pathways. Cell death & disease. 2019; 10(10):1-7.
77. Hardeland R. Melatonin and inflammation—Story of a double‐edged blade. Journal of pineal research. 2018; 65(4):e12525.
78. Carrillo-Vico A, Lardone PJ, Álvarez-Sánchez N, Rodríguez-Rodríguez A, Guerrero JM. Melatonin: buffering the immune system. International journal of molecular sciences. 2013; 14(4):8638-8683.
79. Kumar Rajendran N, George BP, Chandran R, Tynga IM, Houreld N, Abrahamse H. The influence of light on reactive oxygen species and NF-кB in disease progression. Antioxidants. 2019; 8(12):640.
80. Yang S, Lian G. ROS and diseases: Role in metabolism and energy supply. Molecular and cellular biochemistry. 2020; 467(1):1-2.
81. Harrington BS, Annunziata CM. NF-κB signaling in ovarian cancer. Cancers. 2019; 11(8):1182.
82. Qiu X, Wang X, Qiu J, Zhu Y, Liang T, Gao B, Wu Z, Lian C, Peng Y, Liang A, Su P. Melatonin rescued reactive oxygen species-impaired osteogenesis of human bone marrow mesenchymal stem cells in the presence of tumor necrosis factor-alpha. Stem cells international. 2019; 2019: 6403967.
83. Sobolewski C, Cerella C, Dicato M, Ghibelli L, Diederich M. The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. International journal of cell biology. 2010; 2010.
84. Sheng J, Sun H, Yu FB, Li B, Zhang Y, Zhu YT. The role of cyclooxygenase-2 in colorectal cancer. International journal of medical sciences. 2020; 17(8):1095-1101.
85. Liu B, Qu L, Yan S. Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer cell international. 2015; 15(1):1-6.
86. Ortiz-Franco M, Planells E, Quintero B, Acuña-Castroviejo D, Rusanova I, Escames G, Molina-López J. Effect of melatonin supplementation on antioxidant status and DNA damage in high intensity trained athletes. International journal of sports medicine. 2017; 38(14):1117-1125.
87. Ramli NZ, Yahaya MF, Tooyama I, Damanhuri HA. A mechanistic evaluation of antioxidant nutraceuticals on their potential against age-associated neurodegenerative diseases. Antioxidants. 2020; 9(10):1019.
88. Hardeland R. Melatonin, noncoding RNAs, messenger RNA stability and epigenetics—evidence, hints, gaps and perspectives. International journal of molecular sciences. 2014; 15(10):18221-18252.
89. Konturek PC, Burnat G, Brzozowski T, Zopf Y, Konturek SJ. Tryptophan free diet delays healing of chronic gastric ulcers in rat. J Physiol Pharmacol. 2008; 59(Suppl 2):53-65.
90. Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. International journal of molecular sciences. 2019; 20(23):6008.
91. Hong L, Wang S, Li W, Wu D, Chen W. Tumour-associated macrophages promote the metastasis of ovarian carcinoma cells by enhancing CXCL16/CXCR6 expression. Pathology-Research and Practice. 20181; 214(9):1345-1351.
92. Liu S, Lee JS, Jie C, Park MH, Iwakura Y, Patel Y, Soni M, Reisman D, Chen H. HER2 overexpression triggers an IL1α proinflammatory circuit to drive tumorigenesis and promote chemotherapy resistance. Cancer research. 2018; 78(8):2040-2051.
93. Reiter RJ, Rosales-Corral SA, Tan DX, Acuna-Castroviejo D, Qin L, Yang SF, Xu K. Melatonin, a full service anti-cancer agent: inhibition of initiation, progression and metastasis. International journal of molecular sciences. 2017; 18(4):843.
94. Roane BM, Arend RC, Birrer MJ. Targeting the transforming growth factor-beta pathway in ovarian cancer. Cancers. 2019; 11(5):668.
95. Zhang Y, Alexander PB, Wang XF. TGF-β family signaling in the control of cell proliferation and survival. Cold Spring Harbor perspectives in biology. 2017; 9(4):a022145.
96. Chen J, Gingold JA, Su X. Immunomodulatory TGF-β signaling in hepatocellular carcinoma. Trends in molecular medicine. 2019; 25(11):1010-1023.
97. Bu S, Wang Q, Sun J, Li X, Gu T, Lai D. Melatonin suppresses chronic restraint stress-mediated metastasis of epithelial ovarian cancer via NE/AKT/β-catenin/SLUG axis. Cell death & disease. 2020; 11(8):1-7.
98. Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: causes, consequences, challenges and opportunities. Cellular and Molecular Life Sciences. 2020; 77(9):1745-1770.
99. Hwang C, Heath EI. Angiogenesis inhibitors in the treatment of prostate cancer. Journal of hematology & oncology. 2010; 3(1):1-2.
100. Bhullar KS, Lagarón NO, McGowan EM, Parmar I, Jha A, Hubbard BP, Rupasinghe HV. Kinase-targeted cancer therapies: progress, challenges and future directions. Molecular cancer. 2018; 17(1):1-20.
101. Aguilar-Cazares D, Chavez-Dominguez R, Carlos-Reyes A, Lopez-Camarillo C, Hernadez de la Cruz ON, Lopez-Gonzalez JS. Contribution of angiogenesis to inflammation and cancer. Frontiers in oncology. 2019; 9:1399.
102. González A, Alonso-González C, González-González A, Menéndez-Menéndez J, Cos S, Martínez-Campa C. Melatonin as an Adjuvant to Antiangiogenic Cancer Treatments. Cancers. 2021; 13(13):3263.
103. Krock BL, Skuli N, Simon MC. Hypoxia-induced angiogenesis: good and evil. Genes & cancer. 2011; 2(12):1117-1133.
104. Ziello JE, Jovin IS, Huang Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. The Yale journal of biology and medicine. 2007; 80(2):51-60.
105. Samanta S, Dassarma B, Jana S, Rakshit S, Saha SA. Hypoxia Inducible Factor-1 (HIF-1) and Cancer Progression: A Comprehensive Review. Indian J Cancer Edu Res. 2018:6(1):94-109.
106. Al‐Husein B, Abdalla M, Trepte M, DeRemer DL, Somanath PR. Antiangiogenic therapy for cancer: an update. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2012; 32(12):1095-1111.
107. Dong S, Wu X, Xu Y, Yang G, Yan M. Immunohistochemical study of STAT3, HIF-1α and VEGF in pterygium and normal conjunctiva: Experimental research and literature review. Molecular Vision. 2020; 26:510-516.
108. Martincuks A, Li PC, Zhao Q, Zhang C, Li YJ, Yu H, Rodriguez-Rodriguez L. CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3. Frontiers in Oncology. 2020; 10:2551.
109. Park SY, Jang WJ, Yi EY, Jang JY, Jung Y, Jeong JW, Kim YJ. Melatonin suppresses tumor angiogenesis by inhibiting HIF‐1α stabilization under hypoxia. Journal of pineal research. 2010; 48(2):178-184.
110. Wang R-X, Liu H, Xu L, Zhang H, Zhou R-X (2015) Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells. Oncol Rep 34:2541–2546.
111. Zhang Y, Liu Q, Wang F, Ling EA, Liu S, Wang L, Yang Y, Yao L, Chen X, Wang F, Shi W. Melatonin antagonizes hypoxia‐mediated glioblastoma cell migration and invasion via inhibition of HIF‐1α. Journal of pineal research. 2013; 55(2):121-130.
112. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Science advances. 2016; 2(5):e1600200.
113. Cutruzzolà F, Giardina G, Marani M, Macone A, Paiardini A, Rinaldo S, Paone A. Glucose metabolism in the progression of prostate cancer. Frontiers in physiology. 2017; 8:97.
114. Rudlowski C, Moser M, Becker AJ, Rath W, Buttner R, Schroder W, Schurmann A. GLUT1 mRNA and protein expression in ovarian borderline tumors and cancer. Oncology. 66(5):404-410.
115. Ma Y, Wang W, Idowu MO, Oh U, Wang XY, Temkin SM, Fang X. Ovarian cancer relies on glucose transporter 1 to fuel glycolysis and growth: anti-tumor activity of BAY-876. Cancers. 2019; 11(1):33.
116. Mayo JC, Cernuda R, Quiros I, Rodriguez P, Garcia JI, Hevia D, Sainz RM. Understanding the role of melatonin in cancer metabolism. Melatonin Research. 2019; 2(3):76-104.
117. Phadngam S, Castiglioni A, Ferraresi A, Morani F, Follo C, Isidoro C. PTEN dephosphorylates AKT to prevent the expression of GLUT1 on plasmamembrane and to limit glucose consumption in cancer cells. Oncotarget. 2016; 7(51):84999- 85020.
118. Tuomi, T., et al. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell metab. 2016;23(6):1067–1077.
119. Schettig R, Sears T, Klein M, Tan-Lim R, Matthias R, Aussems C, Hummel M, Sears R, Poteet Z, Warren D, Oertle J. Melatonin: A Powerful Integrative Adjunctive Agent for Oncology. Journal of Cancer Therapy. 2020; 11(9):571-596.
120. Mihandoost E, Shirazi A, Mahdavi SR, Aliasgharzadeh A. Can melatonin help us in radiation oncology treatments?. BioMed research international. 2014 11; 2014.
121. Chung SI, Smart DK, Chung EJ, Citrin DE. Radioprotection as a method to enhance the therapeutic ratio of radiotherapy. Increasing the therapeutic ratio of radiotherapy. 2017:79-102.
122. Farhood B, Goradel NH, Mortezaee K, Khanlarkhani N, Najafi M, Sahebkar A. Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment. Journal of cellular physiology. 2019; 234(5):5613-5627.
123. Barberino RS, Menezes VG, Ribeiro AE, Palheta Jr RC, Jiang X, Smitz JE, Matos MH. Melatonin protects against cisplatin-induced ovarian damage in mice via the MT1 receptor and antioxidant activity. Biology of reproduction. 2017; 96(6):1244-1255.
124. Plaimee P, Weerapreeyakul N, Barusrux S, Johns NP. Melatonin potentiates cisplatin‐induced apoptosis and cell cycle arrest in human lung adenocarcinoma cells. Cell proliferation. 2015; 48(1):67-77.
125. Futagami M, Sato S, Sakamoto T, Yokoyama Y, Saito Y. Effects of melatonin on the proliferation and cis-diamminedichloroplatinum (CDDP) sensitivity of cultured human ovarian cancer cells. Gynecologic oncology. 2001; 82(3):544-549.
126. Kleszczyński K, Zwicker S, Tukaj S, Kasperkiewicz M, Zillikens D, Wolf R, Fischer TW. Melatonin compensates silencing of heat shock protein 70 and suppresses ultraviolet radiation‐induced inflammation in human skin ex vivo and cultured keratinocytes. Journal of pineal research. 2015; 58(1):117-126.
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How to Cite
Das, N. K., and S. Samanta. “ The Promising Oncostatic Effects of Melatonin Against Ovarian Cancer: Melatonin and Ovarian Cancer”. World Journal of Current Medical and Pharmaceutical Research, Vol. 3, no. 4, Aug. 2021, pp. 85-93, doi:10.37022/wjcmpr.v3i4.185.
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