4-Acetylantroquinonol B Isolated from Antrodia cinnamomea Arrests Proliferation of Human Hepatocellular Carcinoma HepG2 Cell by Affecting p53, p21 and p27 Levels

摘要

The 4-acetylantroquinonol B isolated from the mycelium of Antrodia cinnamomea could inhibit proliferation of hepatocellular carcinoma cells HepG2 with IC_(50) 0.1μg/mL. When the HepG2 cells were treated with 4-acetylantroquinonol B for 72 h, the proportion of cells in the Gl phase of the cell cycle increased and that in the S phase decreased significantly, and the proportion of G2/M phase cells were not obviously changed. In addition, the 4-acetylantroquinonol B treatment resulted in the decreases of CDK2 and CDK4, and an increase of p27 in a dose-dependent manner. The protein levels of p53 and p21 proteins were also increased when the cells were treated with low dosage (0.1μg/mL) of 4-acetylantroquinonol B, Higher dosages, however, decreased the expression of pS3 and p21 proteins. Assay of RT-PCR indicated that, corresponding to the increases of p53 and p21 proteins at the dosage of 0.1 μg/mL, the mRNAs of pS3 and p21 showed 1.66- and 1.61-fold upregulations, respectively. Corresponding to the decreases of CDK2 and CDK4 proteins, the mRNAs of CDK2 and CDK4 showed -1.02- and -1.13-fold downregulations, respectively. However, level of p27 mRNA showed -1.2-fold downregulation in spite of the increase in p27 protein. This observation, again, confirms the fact that the p27 gene rarely undergoes homozygous inactivation in cancer cells. Our finding suggested that the 4-acetylantroquinonol B inhibits proliferation of HepG2 cells via affecting pS3, p21 and p27 proteins, and can be considered as a potential cancer drag.