Panaxydol, a polyacetylene compound isolated from Panax ginseng, exerts anti-proliferative effects against malignant cells. No previous study, however, has been reported on its effects on
hepatocellular carcinoma cells. Here, we investigated the effects of
panaxydol on the proliferation and differentiation of human hepatocarcinoma cell line HepG2. We studied by electronic microscopy of morphological and ultrastructural changes induced by
panaxydol. We also examined the cytotoxicities of
panaxydol against HepG2 cells using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium
bromide assay and the effect of
panaxydol on cell cycle distributions by flow cytometry. We investigated the production of liver
proteins in
panaxydol-treated cells including
alpha-fetoprotein and
albumin and measured the specific activity of
alkaline phosphatase and gamma-glutamyl
transferase. We further investigated the effects of
panaxydol on the expression of Id-1,
Id-2, p21 and pRb by RT-PCR or immunoblotting analysis. We found that
panaxydol inhibited the proliferation of HepG2 cells and caused morphological and ultrastructural changes in HepG2 cells resembling more mature forms of hepatocytes. Moreover,
panaxydol induced a cell cycle arrest at the G(1) to S transition in HepG2 cells. It also significantly decreased the secretion of
alpha-fetoprotein and the activity of gamma-glutamyl
transferase. By contrast,
panaxydol remarkably increased the secretion of
albumin and the
alkaline phosphatase activity. Furthermore,
panaxydol increased the
mRNA content of p21 while reducing that of Id-1 and
Id-2.
Panaxydol also increased the
protein levels of p21, pRb and the hypophosphorylated pRb in a dose-dependent manner. These findings suggest that
panaxydol is of value for further exploration as a potential anti-
cancer agent.