Journals / İstanbul Journal of Pharmacy / 2021 / Cilt: 51 - Sayı: 2

In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin

Pages
167–174
Publication Date
2021-08-31
DOI
—
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

This study provides important information that metformin may play an essential role in apoptosis and cell cycle progression in carcinoma cell lines, which can explain the anticancer effects of metformin, but further studies are needed to support these results.

📌 3 Key Takeaways

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Objective & Hypothesis:Background and Aims: Recent studies have shown the anticancer properties of metformin, which is widely used in diabetes mellitus.
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Key Findings & Data:We aimed to investigate the cytotoxic, genotoxic, and apoptotic effects of metformin in HepG2 and HeLa cells.
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Conclusion & Impact:This study provides important information that metformin may play an essential role in apoptosis and cell cycle progression in carcinoma cell lines, which can explain the anticancer effects of metformin, but further studies are needed to support these results.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Metformin · genotoxicity · apoptosis

Abstract

Background and Aims: Recent studies have shown the anticancer properties of metformin, which is widely used in diabetes mellitus. The possible mechanisms of anticancer effects of metformin have not been fully elucidated. We aimed to investigate the cytotoxic, genotoxic, and apoptotic effects of metformin in HepG2 and HeLa cells. Methods: The cytotoxicity, genotoxicity, and apoptotoic effects were determined by MTT method, Comet assay, and FACS assay, respectively. Results: Metformin significantly decreased cell viability above 4 and 32 mM in HepG2 and HeLa cells, respectively, for 48 h. The IC50 values were 57.3 mM (HepG2) and 76.9 mM (HeLa). Metformin (5-1000 μM) alone did not increase DNA damage in all cells. It did not change oxidative DNA damage in HepG2 cells but induced oxidative DNA damage in HeLa cells. HepG2 cells treated with only 32 mM metformin revealed 10% apoptosis. G0/G1 phase accumulation was statistically higher in the cells treated with 4, 8, and 64 mM metformin (91%, 99%, and 97% respectively) than in (-) control (80%). HeLa cells revealed apoptosis of 30%, 39%, 27% at 4, 32, and 64 mM concentrations, respectively. The results implicate that the inhibition of HepG2 cell viability may be due to the arrest of cell cycle in G0/G1 phase and apoptosis, whereas apoptotic response is mainly responsible for the cytotoxicity of metformin in HeLa cells. Conclusion: Metformin may not induce DNA damage at non-cytotoxic high doses and lead to apoptosis, even if compatible with previous data. This study provides important information that metformin may play an essential role in apoptosis and cell cycle progression in carcinoma cell lines, which can explain the anticancer effects of metformin, but further studies are needed to support these results.

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Cite This Article

SARIAYDIN, T., ÇAL, T., DİLSİZ, S. A., CANPINAR, H., BUCURGAT, Ü. Ü. (2021). In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin. İstanbul Journal of Pharmacy, Cilt: 51 - Sayı: 2, 167–174. https://ajindex.com/articles/676249

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References (1)

  1. Algire, C., Moiseeva, O., Deschênes-Simard, X., Amrein, L., Petruccelli, L., Birman, E., Viollet, B., Ferbeyre, G. & Pollak, M. N. (2012). Metformin reduces endogenous reactive oxygen species and associated DNA damage. Cancer Prevention Research, 5(4), 536-543. • Amador, R. R., Longo, J. P. F., Lacava, Z.G., Dórea, J. G. & Almeida Santos, M. F. M. (2012). Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells. Genetics and Molecular Biology, 35(1), 153-158. • Attia, S. M., Helal, G. K., & Alhaider, A. A. (2009). Assessment of genomic instability in mormal and diabetic rats treated with metformin. Chemico-Biological Interactions, 180(2), 296-304. • Ben Sahra, I., Laurent, K., Loubat, A., Giorgetti-Peraldi, S., Colosetti, P., Auberger, P., Tanti, J. F., Le Marchand-Brustel, Y., & Bost, F. (2008). The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene, 27, 3576-3586. • Cai, X., Hu, X., Cai, B., Wang, Q., Li, Y., Tan, X. … Jing, X. (2013). Metformin suppresses hepatocellular carcinoma cell growth through induction of cell cycle G1/G0 phase arrest and p21CIP and p27KIP expression and downregulation of cyclin D1 in vitro and in vivo. Oncology Reports, 30(5), 2449-2457. • Cai, X., Hu, X., Tan, X., Cheng, W., Wang, Q., Chen, X., Guan, Y., Chen, C., & Jing, X. (2015). Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo. PLoS One, 10(7), e0133349. • Colquhoun, A. J., Venier, N. A., Vandersluis, A. D., Besla, R., Sugar, L. M., Kiss, A. …Venkateswaran, V. (2012). Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer. Prostate Cancer and Prostatic Diseases, 15(4), 346-352. • Dombrowski, F., Mathieu, C., & Evert, M. (2006). Hepatocellular neoplasms induced by low-number pancreatic islet transplants in autoimmune diabetic BB/Pfd rats. Cancer Research, 66(3), 1833- 1843. • Donadon, V., Balbi, M., Casarin, P., Vario, A., & Alberti, A. (2008). Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy: Potential role of insulin. World Journal of Gastroenterology, 14(37), 5695-5700. • Giovannucci, E. & Michaud, D. (2007). The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology, 132(6), 2208-2225. • Jalving, M., Gietema, J. A., Lefrandt, J. D., de Jong, S.,