Effects of aqueous extract of Sophora flavescens on the expression of cell cycle regulatory proteins in human oral mucosal fibroblasts.

Sophorae Radix, the dried roots of Sophora flavescens AITON (Leguminosae), has been used in Oriental traditional medicine for treatment of skin and mucosal ulcers, sores, gastrointestinal hemorrhage, diarrhea, inflammation and arrhythmia. In the present study, we examine the effect of the aqueous extract of Sophorae Radix (AESR) on cell proliferation and cell cycle regulation in human oral mucosal fibroblasts (HOMFs). To study the molecular mechanisms of cell cycle regulation by AESR, we also measured the intracellular levels of cell cycle regulatory proteins such as cyclin D, cyclin-dependent kinases (CDK)-4, CDK-6, cyclin E, CDK-2, p53, p21WAF1/CIP1 and p16INK4A. Cell proliferation was increased in the presence of 10 approximately 500 microg/ml of AESR. Maximal growth stimulation was observed in those cells exposed to 100 microg/ml of AESR. Exposure of HOMFs to 100 microg/ml of AESR resulted in an increase of cell cycle progression. The levels of cyclin E and CDK-2 were increased in HOMFs after 100 microg/ml of AESR treatment, but the levels of cyclin D, CDK-4, and CDK-6 were unchanged. After exposure to 100 microg/ml of AESR, the protein levels of p16INK4A and p53 were decreased as compared to that of the control group, but the level of p21WAF1/CIP1 was similar in the cells treated with 100 microg/ml of AESR and untreated cells. The results suggest that AESR may increase cell proliferation and cell cycle progression in HOMFs, which is linked to increased cellular levels of cyclin E and CDK-2 and decreased cellular levels of p53 and p16INK4A. Further studies are necessary to clarify the active constituents of AESR responsible for such biomolecular activities.