Cordycepin re-sensitizes multidrug resistance cancer cells to chemotherapeutic agents through modulating P-glycoprotein expression and ATPase function

Abstract

Multidrug resistance (MDR) cancer is one of the major issues in systemic chemotherapy. Development of MDR reversal agents from natural products has been considered as a potential and safe solution. The present study aimed at investigating whether cordycepin, a major constituent in dietary mushrooms, exhibited MDR reversal effect and the mechanisms of kinetic interactions were further explored. Treatment of cordycepin not only modulated the expression of human P-glycoprotein (P-gp), but inhibited P-gp function through stimulating P-gp ATPase activity in cells that stably expressed human P-gp (ABCB1/Flp-InTM-293) and in MDR cancer cells (KB-vin) without influencing cell viability. The molecular docking model demonstrated that cordycepin may interact with P-gp by hydrogen bonds at the nucleotide binding domain. Furthermore, cordycepin significantly re-sensitized MDR cancer cells (KB-vin, HepG2-vin and NCI-H460/MX20) to conventional chemotherapeutic agents, such as paclitaxel and mitoxantrone. These findings suggest a promising combination use of cordycepin with chemotherapeutic agents in cancer treatment.

Keywords

• Cordycepin
• Multidrug resistant cancer
• P-glycoprotein
• Mushrooms
• Cancer treatment