Anti-tumor Effect of Gambogenic Acid and Its Effect on CYP2C and CYP3A after Oral Administration

Abstract

Gambogenic acid (GNA), which has a broad spectrum of anti-tumor activity, is considered as a potential anticancer ingredient. In this study, we examined the antitumor effect and the effect of GNA on cytochrome P450 and pregnane X receptor (PXR).In anti-tumor experiments, an A549 cells tumor-bearing nude mice model was established. Tumor weights and volumes were measured. Inhibition ratio (IR) was calculated. In a pharmacokinetic study, after intragastrical administration of GNA in rats, a cocktail method was adopted to evaluate the activities of CYP2C6, 2C11 and 3A1; RT-qPCR and WB assays were applied to evaluate the mRNA and protein expression levels, respectively. Compared with injection, oral administration also can inhibit tumor growth. Moreover, GNA increased the activities of CYP2C11 and CYP3A1 in the high-dose group as well as the mRNA and protein expression levels.The mRNA and protein expression levels of PXR were also slightly induced. Our study suggested that, oral administration of GNA was effective in inhibiting tumor growth in mice and could induced the activities of CYP2C and CYP3A in rats.

Unveiling Gambogenic Acid as a Promising Antitumor Compound: A Review

“…The cytochrome P450 (CYP450) superfamily is usually considered the most important phase I drug-metabolizing enzyme system. GNA increased the activity of liver CY-P1A2, CYP2E1, CYP2C, and CYP3A [86,87]. Therefore, when GNA is administered with other drugs, potential drug-drug interactions mediated by CYP1A2, CYP2E1, CYP2C, and CYP3A induction should be taken into consideration.…”