Role of metformin on base excision repair pathway in p53 wild-type H2009 and HepG2 cancer cells.

Abstract:

:The antidiabetic agent metformin was shown to further possess chemopreventive and chemotherapeutic effects against cancer. Despite the advances, the underlying molecular mechanisms involved in decreasing tumor formation are still unclear. The understanding of the participation of oxidative stress in the action mechanism of metformin and its related effects on p53 and on DNA base excision repair (BER) system can help us to get closer to solve metformin puzzle in cancer. We investigated the effects of metformin in HepG2 and H2009 cells, verifying cytotoxicity, oxidative stress, antioxidant status, and DNA BER system. Our results showed metformin induced oxidative stress and reduced antioxidant capacity. Also, metformin treatment with hydrogen peroxide (H2O2) enhanced these effects. Although DNA BER enzyme activities were not changed accordantly together by metformin as a single agent or in combination with H2O2, activated p53 was decreased with increased oxidative stress in H2009 cells. Our study on the relationship between metformin/reactive oxygen species and DNA BER system in cancer cells would be helpful to understand the anticancer effects of metformin through cellular signal transduction pathways. These findings can be a model of the changes on oxidative stress that reflects p53's regulatory role on DNA repair systems in cancer for the future studies.

journal_name

Hum Exp Toxicol

authors

Dogan Turacli I,Candar T,Yuksel BE,Demirtas S

doi

10.1177/0960327117737145

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

909-919

issue

9

eissn

0960-3271

issn

1477-0903

journal_volume

37

pub_type

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