Ganoderenic acid B, a natural product derived from Ganoderma lucidum, can work by inhibiting the transport function of ABCB1 and enhancing the cytotoxicity of chemotherapy drugs against AbCB1-mediated multidrug resistant cancer cells.

Ganoderenic acid B, a lanostane-type triterpene isolated from Ganoderma lucidum, exhibited potent reversal effect on ABCB1-mediated multidrug resistance of HepG2/ADM cells to doxorubicin, vincristine and paclitaxel. Similarly, Ganoderenic acid B could also significantly reverse the resistance of ABCB1-overexpressing MCF-7/ADR cells to doxorubicin. Furthermore, Ganoderenic acid B notably enhanced intracellular accumulation of rhodamine-123 in HepG2/ADM cells through inhibition of its efflux. ABCB1 siRNA interference assay indicated that the reversal activity of Ganoderenic acid B was dependent on ABCB1. Further mechanistic investigations found that Ganoderenic acid B did not alter the expression level of ABCB1 and the activity of ABCB1 ATPase. Molecular docking model displayed that the positions of Ganoderenic acid B binding to ABCB1 were different from the region of verapamil interacted with ABCB1. Ganoderenic acid B can enhance the cytotoxicity of chemotherapeutics towards ABCB1-mediated MDR cancer cells via inhibition of the transport function of ABCB1. These findings provide evidence that Ganoderenic acid B has the potential to be developed into an ABCB1-mediated multidrug resistance reversal agent.[1]