1,25-Dihydroxyvitamin D 3 induced cell cycle arrest in the human primary liver cancer cell line HepG2

Abstract

The inhibitory effect of 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2D 3) on the proliferation of a number of human and rat liver cancer cell lines has recently been reported. In this study we have demonstrated that these cell lines express functional receptors able to specifically bind [ 3H]1,25-(OH) 2D 3. The highest level of functional receptor were found in the human liver cancer cell line HepG2 which had previously been shown to be the most sensitive in 1,25-(OH) 2D 3 growth inhibition assays. The identity of the binding protein with the Vitamin D3 receptor was confirmed by PCR analysis of HepG2 cell mRNA. Additionally, the inhibitory effect of 1,25-(OH) 2D 3 on growth of the human liver cancer cell line HepG2 resulted from arrest in the G0/G1 phase of the cell cycle. Increases in the fraction of cells in G0/G1 were dependent upon the concentration of 1,25-(OH) 2D 3 and were accompanied by complementary decreases in the number of cells in S phase. There was no change in the number of cells in G2+M at any concentration of the hormone. Clonal growth of HepG2 cells in response to 1,25-(OH) 2D 3 was also dose dependent over three orders of magnitude, thus indicating heterogeneity in cell cycle arrest by this hormone.