Myricetin modulates the cytotoxicity and genotoxicity of oxaliplatin: protective potential and biological risks

Myricetin (ME) is a flavonoid found in various plant-based foods, recognized for its anti-inflammatory, antioxidant, and anticancer properties. This study evaluated the antiproliferative and antimutagenic potential of ME, both isolated and in combination with the chemotherapeutic agent oxaliplatin (OXL), using in vitro models. Cytotoxicity was assessed in the NCI-H460 non-small cell lung cancer cell line via the MTT assay, while the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay was performed in CHO-K1 non-tumoral cells to investigate chromosomal instability and cytostasis. ME at concentrations of 5 and 10 µM significantly reduced the viability of NCI-H460 cells, demonstrating a cytotoxic effect. OXL alone also reduced cell viability; however, when combined with ME, this effect was attenuated, suggesting a protective or antagonistic interaction. In CHO-K1 cells, ME did not modulate cytostasis induced by OXL in any treatment protocol. Regarding genotoxicity, ME failed to reduce chromosomal damage markers (micronuclei, nucleoplasmic bridges, and nuclear buds) when administered before or simultaneously with OXL. Interestingly, post-treatment with ME significantly increased the frequency of micronuclei induced by OXL, indicating a potentiating effect. These findings suggest that although ME possesses antiproliferative activity against tumor cells, it may also interfere with the efficacy of OXL depending on the treatment schedule. The results contribute to understanding the dual role of phytochemicals in chemotherapy, emphasizing the importance of evaluating timing and interaction in combination therapies.