α-Mangostin enhances cisplatin activity in drug-resistant breast cancer cells by targeting multidrug resistance-associated protein 2

Cisplatin resistance presents a significant challenge in breast cancer treatment, often resulting in therapy failure and relapse. The overexpression of multidrug resistance-associated protein (MRP) in breast cancer cells contributes to chemotherapy resistance. Combining cisplatin with other anti-cancer agents has improved its efficacy in overcoming resistance in cancer cells. This study developed cisplatin-resistant breast cancer cell lines, CIS/MCF-7 and CIS/ MDA-MB-231, derived from the MCF-7 and MDA-MB-231 parental lines. These resistant cell lines exhibited altered morphology and significant resistance to cisplatin, with resistance indices of 1.99 and 6.03, respectively. Combining the natural compound α-mangostin (AMG) with 30 μM cisplatin significantly enhanced the cisplatin effect on cell viability in cisplatin-resistant cell lines in a dose-dependent manner. The overexpression of the MRP2 gene in CIS/MDA-MB-231 cells suggests their potential roles in cisplatin resistance. Molecular docking revealed a favorable interaction between AMG and MRP2, suggesting a possible mechanism by which AMG enhances cisplatin activity. Our findings indicate that AMG can improve cisplatin efficacy in chemotherapy-resistant breast cancers, possibly by targeting MRP2 induction.