Effects of ferulic acid and isoferulic acid on proliferation of HepG2 cells and its cytochrome P450 enzymes / 中草药

ABSTRACT

Objective: To observe the action characteristics of ferulic acid and isoferulic acid on cytochrome P450 isoenzymes1A1 and 3A4 (CYP1A1, CYP3A4) in HepG2 cells. Methods: MTT colorimetry was used to investigate the effects of ferulic acid and isoferulic acid at different concentration on the proliferation of in vitro cultured HepG2 cells. Flow cytometry was used to determine the effects of ferulic acid and isoferulic acid on cell cycle of human liver HepG2 cells; The expression of CYP1A1 and CYP3A4 mRNA was tested by real time quantitative PCR technology after drug treatment and then CYP3A4 protein expression was detected by protein immunoblot method (Western blotting). Results: HepG2 cells were inhibited by ferulic acid and isoferulic acid after 48 h action, with a clear dose-response relationship; Two drugs (50 μg/mL) blocked HepG2 cell cycle in G2-M phase; All of the concentration (100, 50, and 25 μg/mL) of the two drugs were CYP1A1 and CYP3A4 mRNA inhibitors; After cells were disposed by the two kinds of drugs (50 μg/mL) with 48 h, protein expression was significantly lower than that in the control group; And compared with the control group, the expression amounts of ferulic acid and isoferulic acid were 0.57 and 0.39. Conclusion: The proliferation of HepG2 cells is inhibited by the two drugs, and the cell cycle was arrested at G2/M phase, which that may be one of its mechanisms, so as to inhibit the mRNA expression of CYP1A1 and CYP3A4. At the same time, both of them could inhibit the protein expression of CYP3A4, as well as the effect degree of difference is bigger, which may be associated with its hydroxyl and the methoxyl isomerisation.