Metformin reduces the cellular DNA repair capacity and enhances the effect of curcumin on the induction of apoptosis in AGS gastric cancer cells

Abstract

BackgroundCancer results from the accumulation of mutations in critical genes, such as DNA repair genes. But these genes are a double-edged sword, because the basis of current cancer treatment is DNA damage from chemotherapy and radiation, and the repair system can slow the healing process by repairing the induced damage. Therefore, any substance that can reduce the DNA repair capacity of cancer cells can make the cells more sensitive to treatment. Metformin and curcumin, as low-complication compounds, can play this role well.MethodsIn the present work, changes in the expression of CASP3, BAX, and BCL2L1 apoptotic genes, and nine genes involved in DNA repair pathways (XRCC1, XRCC2, XRCC3, XRCC4, XRCC5, XRCC6, XRCC7, BRCA1 and BRAC2) were measured comparatively by real-time PCR in AGS gastric cancer cell line under single and co-treatments with metformin and curcumin.ResultsOur findings showed that co-treatment of metformin and curcumin induced decreasing the expression of anti-apoptotic BCL2L1 and increasing expression of proapoptotic CASP3 and BAX. Metformin decreased the expression levels of seven genes, while curcumin did not alter the expression levels. The co-treatment of metformin and curcumin showed that although the XRCC2, XRCC3, XRCC4, XRCC5, XRCC6, XRCC7, BRCA1, and BRCA2 were down-regulated, there was no difference between metformin and co-treatment for mRNA levels.ConclusionOur results suggest that metformin increases the sensitivity of cancer cells to anticancer drugs by suppressing several DNA repair pathways and that curcumin may induce apoptosis.