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Fatemeh Yari1 
, Zynab Sadeghi ghadi2 , Hossien Mahbodi3 , Seyed Ehsan Enderami2 , Kimia Zargari1 , Mehryar Zargari *4
, Zynab Sadeghi ghadi2 , Hossien Mahbodi3 , Seyed Ehsan Enderami2 , Kimia Zargari1 , Mehryar Zargari *4
1- Department of clinical biochemistry and genetic, Mazandaran University of Medical Sciences, Sari, Iran.
2- Department of biotechnology, faculty of advanced technology in medicine, Mazandaran University of medical sciences, sari, Iran
3- Depatment of of Biotechnology, Alborz University of Medical Sciences, Karaj, Iran.
4- Professor of Biochemistry, Department of clinical biochemistry and genetic, Molecular and cell biology research center, Faculty of Medicine Mazandaran University of Medical Sciences, Sari, Iran. ,mzargari@mazums.ac.ir
2- Department of biotechnology, faculty of advanced technology in medicine, Mazandaran University of medical sciences, sari, Iran
3- Depatment of of Biotechnology, Alborz University of Medical Sciences, Karaj, Iran.
4- Professor of Biochemistry, Department of clinical biochemistry and genetic, Molecular and cell biology research center, Faculty of Medicine Mazandaran University of Medical Sciences, Sari, Iran. ,
Abstract: (568 Views)
Background and Objective: Currently, combination drug therapy has emerged as a promising strategy in cancer treatment, as the simultaneous administration of two drugs can enhance therapeutic efficacy and overcome drug resistance. This study aimed to investigate the combined effects of colchicine: microtubule-disrupting alkaloid and melatonin: antioxidant and oncostatic properties on cell viability and expression of apoptosis-related genes (BAX and BCL2) in MCF-7 human breast cancer cell line.
Methods: MCF-7 cells were cultured under standard conditions and treated with colchicine, melatonin, or their combination for 24, 48, and 72 hours. Cell viability was determined using MTT assay and BAX and BCL2 gene expression were quantified by reverse transcription polymerase chain reaction.
Results: The MTT assay at 48 hours revealed IC50 values of 150 µg/ml for colchicine and 371 µg/ml for melatonin. Combination treatment with colchicine (>25 µg/ml) and a fixed concentration of melatonin (150 µg/ml) resulted in a 50% reduction in cell viability (P<0.01). Gene expression analysis showed that colchicine (75 µg/ml), melatonin (250 µg/ml), and their combination (colchicine: 25 µg/ml; melatonin: 150 µg/ml) significantly increased BAX expression and decreased BCL2 expression compared with the control group (P<0.05).
Conclusion: Co-treatment with colchicine and melatonin significantly reduced MCF-7 cell viability and regulated apoptosis-related genes (BAX and BCL2), indicating a synergistic effect. These findings suggest that this combination may represent a promising therapeutic strategy for breast cancer. Further in vivo and clinical studies are required to confirm these findings.
Methods: MCF-7 cells were cultured under standard conditions and treated with colchicine, melatonin, or their combination for 24, 48, and 72 hours. Cell viability was determined using MTT assay and BAX and BCL2 gene expression were quantified by reverse transcription polymerase chain reaction.
Results: The MTT assay at 48 hours revealed IC50 values of 150 µg/ml for colchicine and 371 µg/ml for melatonin. Combination treatment with colchicine (>25 µg/ml) and a fixed concentration of melatonin (150 µg/ml) resulted in a 50% reduction in cell viability (P<0.01). Gene expression analysis showed that colchicine (75 µg/ml), melatonin (250 µg/ml), and their combination (colchicine: 25 µg/ml; melatonin: 150 µg/ml) significantly increased BAX expression and decreased BCL2 expression compared with the control group (P<0.05).
Conclusion: Co-treatment with colchicine and melatonin significantly reduced MCF-7 cell viability and regulated apoptosis-related genes (BAX and BCL2), indicating a synergistic effect. These findings suggest that this combination may represent a promising therapeutic strategy for breast cancer. Further in vivo and clinical studies are required to confirm these findings.
Type of Study: Original Research Article |
Subject:
Clinical Medicine
Received: 2025/09/2 | Accepted: 2026/06/22
Received: 2025/09/2 | Accepted: 2026/06/22
References
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3):209-249. [DOI:10.3322/caac.21660] [PMID]
2. Barbosa AM, Martel F. Targeting glucose transporters for breast cancer therapy: the effect of natural and synthetic compounds. Cancers. 2020; 12(1):154. [DOI:10.3390/cancers12010154] [PMID] [PMCID]
3. Sun Y, Lin X, Chang H. Proliferation inhibition and apoptosis of breast cancer MCF-7 cells under the influence of colchicine. J BUON. 2016; 21(3):570-5.
4. Hawash M. Recent advances of tubulin inhibitors targeting the colchicine binding site for cancer therapy. Biomolecules. 2022; 12(12):1843. [DOI:10.3390/biom12121843] [PMID] [PMCID]
5. Foumani EA, Irani S, Shokoohinia Y, Mostafaie A. Colchicine of Colchicum autumnale, a traditional anti-inflammatory medicine, induces apoptosis by activation of apoptotic genes and proteins expression in human breast (MCF-7) and mouse breast (4T1) cell lines. Cell J. 2022;24(11):647-656.
6. Czarnecka-Czapczyńska M, Przygórzewska A, Dynarowicz K, Bartusik-Aebisher D, Aebisher D, Kawczyk-Krupka A. Glycosaminoglycans targeted by colchicine in MCF-7 cells. Pharmaceutics. 2025;17(11):1368. [DOI:10.3390/pharmaceutics17111368] [PMID]
7. Targhazeh N, Reiter RJ, Rahimi, Qujeq D, Yousefi T, Shahavi MH, et al. Oncostatic activities of melatonin: roles in cell cycle, apoptosis, and autophagy. Biochimie. 2022; 202:34-48. [DOI:10.1016/j.biochi.2022.06.008] [PMID]
8. Talib WH, Alsayed AR, Abuawad A, Daoud S, Mahmod AI. Melatonin in cancer treatment: current knowledge and future opportunities. Molecules. 2021; 26(9):2506. [DOI:10.3390/molecules26092506] [PMID] [PMCID]
9. Schettig R, Sears T, Klein M, Tan-Lim R, Matthias R, Aussems C, et al. Melatonin: a powerful integrative adjunctive agent for oncology. J Cancer Ther. 2020; 11(9):571-596. [DOI:10.4236/jct.2020.119049]
10. Trejo-Solís C, Rojas-Tomé IS, Palomares-Alonso F, Jung-Cook H. Melatonin combined with antineoplastic drugs or natural products for cancer treatment: an update. Curr Res Pharmacol Drug Discov. 2025;9:100239. [DOI:10.1016/j.crphar.2025.100239] [PMID] [PMCID]
11. Talib WH, Sabri SM, Hadi RW, Prémusz V, Beregi T. Melatonin and vitamins: a promising combination to augment conventional anticancer therapies. Nutrients. 2025; 17(19):3120. [DOI:10.3390/nu17193120] [PMID] [PMCID]
12. Oral S, Akpak YK, Turan G, Lafci D, Kinci MF, Usta CS. Efficacy of colchicine and melatonin in the treatment of rat endometriosis model: An animal study. J Reprod Immunol. 2024; 165:104294. [DOI:10.1016/j.jri.2024.104294] [PMID]
13. Shayan S, Osgoei LT, Jouni FJ. Effect of capecitabine and melatonin on HER2+ (SK-BR-3) and HER2- (MCF7) human breast cancer cell lines. Trop J Pharm Res. 2023; 22(7):1387-93. [DOI:10.4314/tjpr.v22i7.5]
14. Alamro AA, Al-Malky MM, Ansari MG, Osama EA, Alnaami AM, Hussain SD, et al. The effects of melatonin and vitamin D3 on the gene expression of BCl-2 and BAX in MCF-7 breast cancer cell line. J King Saud Univ Sci. 2021; 33(2):101287. [DOI:10.1016/j.jksus.2020.101287]
15. Önder GÖ, Sezer G, Özdamar S, Yay A. Melatonin has an inhibitory effect on MCF-7 and MDA-MB-231 human breast cancer cell lines by inducing autophagy and apoptosis. Fundam Clin Pharmacol. 2022; 36(6):1038-56. [DOI:10.1111/fcp.12813] [PMID]
16. Deng S, Krutilina RI, Hartman KL, Chen H, Parke DN, Wang R, et al. Colchicine-binding site agent CH-2-77 as a potent tubulin inhibitor suppressing triple-negative breast cancer. Mol Cancer Ther. 2022; 21(7):1103-14. [DOI:10.1158/1535-7163.MCT-21-0899] [PMID] [PMCID]
17. Kumar A, Singh B, Sharma PR, Bharate SB, Saxena AK, Mondhe DM, et al. A novel microtubule depolymerizing colchicine analogue triggers apoptosis and autophagy in HCT-116 colon cancer cells. Cell Biochem Funct. 2016; 34(2):69-81. [DOI:10.1002/cbf.3166] [PMID]
18. Kong X, Gao R, Wang Z, Wang X, Fang Y, Gao J, et al. Melatonin: a potential therapeutic option for breast cancer. Trends Endocrinol Metab. 2020; 31(11):859-71. [DOI:10.1016/j.tem.2020.08.001] [PMID]
19. Song D, Liu Y, Yao Y, Liu F, Tao W, Zhou X, et al. Melatonin improves bisphenol A-induced cell apoptosis, oxidative stress and autophagy impairment via inhibition of the p38 MAPK signaling pathway in FLK-BLV cells. Environ Toxicol. 2022; 37(7):1551-62. [DOI:10.1002/tox.23505] [PMID]
20. Wang X, Zhong X, Liu Z, Cheng L. Recent progress of chemodynamic therapy-induced combination cancer therapy. Nano Today. 2020; 35:100946. [DOI:10.1016/j.nantod.2020.100946]
21. Sanchez-Barcelo EJ, Mediavilla MD, Alonso-Gonzalez C, Reiter RJ. Melatonin uses in oncology: breast cancer prevention and reduction of side effects of chemotherapy and radiation. Expert Opin Investig Drugs. 2012; 21(6):819-31. [DOI:10.1517/13543784.2012.681045] [PMID]
22. Talib WH. A ketogenic diet combined with melatonin overcomes cisplatin and vincristine drug resistance in breast carcinoma syngraft. Nutrition. 2020; 72:110659. [DOI:10.1016/j.nut.2019.110659] [PMID]
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