Research Article

DOI :10.26650/IstanbulJPharm.2021.0079   IUP :10.26650/IstanbulJPharm.2021.0079    Full Text (PDF)

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

Tuba SarıaydınTuğbagül ÇalSevtap Aydın DilsizHande CanpınarÜlkü Ündeğer Bucurgat

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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Sarıaydın, T., Çal, T., Aydın Dilsiz, S., Canpınar, H., & Ündeğer Bucurgat, Ü. (2021). In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin. İstanbul Journal of Pharmacy, 51(2), 167-174.


Sarıaydın T, Çal T, Aydın Dilsiz S, Canpınar H, Ündeğer Bucurgat Ü. In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin. İstanbul Journal of Pharmacy. 2021;51(2):167-174.


Sarıaydın, T.; Çal, T.; Aydın Dilsiz, S.; Canpınar, H.; Ündeğer Bucurgat, Ü. In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin. İstanbul Journal of Pharmacy, [Publisher Location], v. 51, n. 2, p. 167-174, 2021.

Chicago: Author-Date Style

Sarıaydın, Tuba, and Tuğbagül Çal and Sevtap Aydın Dilsiz and Hande Canpınar and Ülkü Ündeğer Bucurgat. 2021. “In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin.” İstanbul Journal of Pharmacy 51, no. 2: 167-174.

Chicago: Humanities Style

Sarıaydın, Tuba, and Tuğbagül Çal and Sevtap Aydın Dilsiz and Hande Canpınar and Ülkü Ündeğer Bucurgat. In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin.” İstanbul Journal of Pharmacy 51, no. 2 (Sep. 2021): 167-174.

Harvard: Australian Style

Sarıaydın, T & Çal, T & Aydın Dilsiz, S & Canpınar, H & Ündeğer Bucurgat, Ü 2021, 'In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin', İstanbul Journal of Pharmacy, vol. 51, no. 2, pp. 167-174, viewed 24 Sep. 2021,

Harvard: Author-Date Style

Sarıaydın, T. and Çal, T. and Aydın Dilsiz, S. and Canpınar, H. and Ündeğer Bucurgat, Ü. (2021) ‘In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin’, İstanbul Journal of Pharmacy, 51(2), pp. 167-174. (24 Sep. 2021).


Sarıaydın, Tuba, and Tuğbagül Çal and Sevtap Aydın Dilsiz and Hande Canpınar and Ülkü Ündeğer Bucurgat. In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin.” İstanbul Journal of Pharmacy, vol. 51, no. 2, 2021, pp. 167-174. [Database Container],


Sarıaydın T, Çal T, Aydın Dilsiz S, Canpınar H, Ündeğer Bucurgat Ü. In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin. İstanbul Journal of Pharmacy [Internet]. 24 Sep. 2021 [cited 24 Sep. 2021];51(2):167-174. Available from: doi: 10.26650/IstanbulJPharm.2021.0079


Sarıaydın, Tuba - Çal, Tuğbagül - Aydın Dilsiz, Sevtap - Canpınar, Hande - Ündeğer Bucurgat, Ülkü. In vitro assessment of cytotoxic, apoptotic and genotoxic effects of metformin”. İstanbul Journal of Pharmacy 51/2 (Sep. 2021): 167-174.


Published Online31.08.2021


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