Breast cancer is a major global health concern, and resistance to chemotherapy poses a significant challenge. Traditional treatments like tamoxifen (TAM) induce oxidative stress, contributing to chemo-resistance. To enhance treatment effectiveness, exploring complementary options has become a target. Protocatechuic acid (PCA), an antioxidant compound with antitumor properties, has gained attention in this context.

This study evaluated the effect of PCA on MCF7 cell line and its impact on TAM efficacy. It assessed cytotoxicity, cell growth distribution, cell death indicators, reduced glutathione (GSH) levels, its related enzymes, and lactate dehydrogenase (LDH) activities. The combination of PCA and TAM demonstrated antagonistic cytotoxicity equal to 35.8%. Combining PCA with TAM protected against DNA damage in MCF7 cells. It altered cell cycle distribution, increasing cells in the S-phase and decreasing cells in the G2/M phase. The combination treatment also increased early apoptotic cells and reduced viable cells compared to TAM alone. Furthermore, the combination treatment upregulated antioxidant enzymes, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and catalase (CAT), indicate enhanced cellular defense against oxidative damage. Additionally, the combination treatment increased LDH activity.

In conclusion, PCA effectively reduces oxidative stress in MCF7 cells, and combining PCA with TAM shows potential for enhancing treatment outcomes.