Doksorubisin'in neden olduğu genotoksisiteye karşi rosmarinik asit ve epigallokateşin gallat'in koruyucu etkileri

Doxorubicin (Dox) is an anticancer agent that is effective against a variety of human cancers. However, one of the most adverse effects of Dox treatment is its genotoxic effect on normal cells. Antitumor, antioxidant, and antigenotoxic properties of phenolic compounds have been extensively investigated, and their use has expanded significantly in recent years. The phenolic compounds rosmarinic acid (RA) and epigallocatechin gallate (EGCG) are widely seen in plants. In this study, the protective effect of RA and EGCG alone and in combination on Dox induced genotoxicity was investigated with various in vitro test systems, including comet assay, cytokinesis-block micronucleus, and Ames test. It has been shown that free radicals are involved in Dox-induced genotoxicity. For these reasons, the formation of reactive oxygen species was also investigated in this study. Furthermore, the synergistic/antagonistic interaction of these combinations on chemotherapeutic effect of Dox was investigated in breast cancer cell lines. Our results show that EGCG and RA did not exerted genotoxic effect but Dox increased genotoxicity in CHO-K1 and TK6 cells. EGCG and RA significantly reduced the genotoxic effects of Dox in the comet assay, micronucleus, and ames assays. The antioxidant properties of EGCG and RA, as well as their ability to interfere with DNA repair pathways, may be involved in their genoprotective effect. Furthermore, RA decreased the intracellular reactive oxygen species generation in CHO-K1 cells. However, EGCG did not protect against oxidative stress and damaged cells due to its pro-oxidant properties at high concentrations. Dox was more selective against MCF-7 cells, EGCG and RA were found to be more selective against MDA-MB-231 cells. The synergistic effect was observed when EGCG or RA was administered together with Dox to breast cancer cells. In this study, EGCG and RA were found to be effective in decreasing Dox-induced genetic damage as well as inducing Dox's cell viability-reducing effect in breast cancer cells. Key words: Doxorubicin, Rosmarinic acid, Epigallocatechin gallate, Genotoxicity, Chemoprotection.