Ginsenoside exhibits concentration-dependent dual effects on HepG2 cell proliferation via regulation of c-Myc and HNF-4α.

Although ginsenoside can generally promote cell proliferation, it is reported to have anti-proliferative effects in hepatocellular carcinoma (HCC). Whether ginsenoside has concentration-dependent effects on HCC cell proliferation have not been clarified. Transcription factors c-Myc and hepatocyte nuclear factor (HNF)-4α are the most important opposite controllers of HCC cell proliferation. Whether and how ginsenoside regulates c-Myc and HNF-4α as well as their recruitment of the co-activator p300 to exhibit its effects on HCC cell proliferation are pending. In this study, it was found that low concentration ginsenoside promoted HepG2 cell proliferation while high concentration ginsenoside exhibited anti-proliferation effect. For low concentration ginsenoside treatment, c-Myc was up-regulated and the binding of p300 to c-Myc was promoted with obvious co-localization to activate HepG2 cell proliferation. However, for high concentration ginsenoside treatment, besides c-Myc, HNF-4α was also up-regulated might to exhibit an alternative effect. Furthermore, in contrast to the weakened binding and co-localization of c-Myc and p300, the binding of p300 to HNF-4α was enhanced with distinct co-localization to inhibit HepG2 cell proliferation for high concentration ginsenoside treatment. The results manifested that ginsenoside with low and high concentrations may differentially regulate c-Myc and HNF-4α as well as their recruitments of p300, to exhibit concentration-dependent dual effects on HepG2 cell proliferation.