Aloesin up-regulates cyclin E/CDK2 kinase activity via inducing the protein levels of cyclin E, CDK2, and CDC25A in SK-HEP-1 cells.

In the present study, we show that aloesin, which is a low molecular weight ingredients present in Aloe vera, stimulates the proliferation of cultured human hepatoma SK-HEP-1 cells. The incorporation of [3H] thymidine into DNA in the cell cultures was significantly increased at a dose of 10 microM aloesin. The aloesin-induced DNA synthesis appears to require newly synthesized proteins because cycloheximide treatment blocked the DNA synthesis evoked by this compound. We then examined whether this compound increases the intracellular levels of cell cycle regulators by immunoblotting. The data showed that aloesin increased the levels of cyclin E, CDK2, and CDC25A in SK-HEP-1 cells. In addition, immuno-complex kinase assays showed that aloesin up-regulated the enzyme activity of cyclin E/CDK2 kinase in a dose-dependent manner. Collectively, these results suggest that aloesin stimulates the proliferation of SK-HEP-1 cells by inducing the intracellular levels of cyclin E/CDK2 kinase complex and CDC25A, which, together, result in the up-regulation of cyclin E-dependent kinase activity.