Effect of Ginseng on the Expression of the Onco-suppressor Gene p21in Human Breast-Cancer Cell Lines

ABSTRACT

BACKGROUND: Some reports have indicated that ginseng might have an inhibitory effect on tumorogenesis. The p21 protein, a universal cell-cycle inhibitor, directly binds cyclin-CDK complexes. The aim of this study was to determine if ginseng induced p21 mRNA expression in hormone-sensitive (MCF-7) and -insensitive (MDA-MB-231) breast-cancer cell lines. METHODS: Cells were grown in a steroid stripped medium (SSM) and then treated with ginseng extracts, SSM, estradiol (10 9 M), genistein (10 6 M), and cycloheximide (CHX, 10 microgram/ml) for 1 to 48 hours. Northern blot analyses were performed using human p21 cip1 and 36B4 cDNA (control). Cell-cycle analyses using DNA measurements were performed by using 4FACScan flow-cytometry for ginseng extracts and estradiol. RESULTS: p21 mRNA increased in a time- and dose-dependent manner. Ginseng induced peak p21 mRNA expression at 4 hours in MCF-7 and MDA-MB-231 cells (p=0.0004 and p<0.0001, respectively) in comparison with the SSM controls. Neither E2 nor genistein induce p21 expression. CHX, a protein-synthesis inhibitor, did not block the p21 mRNA expression induced by the ginseng extracts, indicating that p21 is induced as an early immediate gene. The ginseng extracts significantly decreased the % S-phase fraction of the cell cycle (p<0.001). CONCLUSIONS: This study suggests that ginseng exhibits growth inhibitory properties due to transcriptional up-regulation of p21.