Rosmarinic acid inhibits the proliferation of ovarian carcinoma cells by activating the p53/BAX signaling pathway

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OBJECTIVE: While chemotherapeutic agents stop the development of cancer cells, they also kill healthy cells. This study aimed to increase anticancer effects and reduce side effects by combining a phytotherapeutic compound with a chemotherapeutic drug. METHODS: This study examined the effects of nine concentrations of rosmarinic acid (RA) and doxorubicin (DOX) on human ovarian adenocarcinoma (OVCAR3) and skin keratinocyte (HaCaT) cell lines. Their cytotoxic effects were assessed based on cell viability, evaluated using the MTT assay, and apoptotic activity, evaluated using NucBlue staining and the gene and protein expression of tumor protein p53 (TP53) and BCL2 associated X, apoptosis regulator (BAX) quantified by qRT-PCR and western blots, respectively. RESULTS: The half-maximal inhibitory concentration after 48 hours was 880.4 μM for RA and 2.26 μM for DOX. The cytotoxicity analysis revealed that cell viability decreased with the RA concentration. RA increased apoptosis in OVCAR3 cells by activating the p53/BAX pathway. Western blots showed that RA and DOX upregulated p53 and BAX protein levels in OVCAR3 cells. CONCLUSIONS: The RA and DOX combination inhibited cell proliferation by inducing apoptosis in OVCAR3 cells. These results suggest that RA may reduce the side effects of DOX toxicity.