Effects of Gambogenic Acid on the Function and Expression of ABCB1 and ABCG2 Transporters in Human HepG2 Liver Cancer cells

In the present study, human HepG2 cells were utilized to evaluate the role of gambogenic acid (GNA) in the function and expression of ABCB1 and ABCG2 transporters. Results of MTT indicated that GNA exhibited the inhibition of the HepG2 cells viability. Functional assays revealed that GNA did not significantly increase the intracellular Rhodamine-123 (Rho-123) and Hoechst33342 accumulation and efflux. Additionally, GNA (0.8 and 1.2 mu g/mL) may significantly downregulate the expression of ABCB1 and ABCG2 mRNA and protein in a dose and time-dependent manner compared with untreated HepG2 cells. Mechanistically, a reduction for the levels of ABCB1 and ABCG2 expression could be related to the downregulation of Pregnane X receptor (PXR) expression while did not affect constitutive androstane receptor (CAR). Collectively, a nontoxic dose of GNA could be a potential inhibitor for ABCB1 and ABCG2 by inhibiting the mRNA and protein expression, and the mechanism, at least in part, was related to the downregulation of PXR expression.