Palmatine sensitizes chemoresistant triple negative breast cancer cells via efflux inhibition of multidrug resistant protein 1.

Abstract

Chemoresistance develops in triple negative breast cancer cells during prolonged therapy with chemotherapeutic drugs, diminishing the benefits of these drugs in breast cancer patients. Palmatine, a natural alkaloid extracted from several medicinal plants in West Africa, has been studied in vitro and found to be a promising anticancer agent for treating triple negative breast cancer. This study seeks to investigate the therapeutic potential of palmatine in sensitizing resistant 4T1 triple negative breast cancer cells to doxorubicin therapy. Cell viability, Hoechst dye membrane transport, intracellular doxorubicin accumulation and Adenosine triphosphatase (ATPase) assays were performed. From the results, the intracellular concentrations of the Hoechst dye and doxorubicin were substantially increased following treatment with palmatine. In addition, palmatine inhibited the doxorubicin efflux activity of the Multidrug resistance protein 1 (MDR1) by stimulating the activity of the ATPase enzymes. A combination of low concentrations of palmatine and verapamil best achieved these results. This research highlights the use of palmatine as a chemosensitizer to aid the treatment of triple negative breast cancer disease.

Keywords

• Chemoresistance
• Palmatine
• Triple negative breast cancer
• multi drug resistant protein