Abstract
American ginseng (AG) has been demonstrated to inhibit breast cancer cell
growth in vitro. p21 protein, a universal cell cycle inhibitor, binds cyclin-CDK
complexes, an important mechanism in cell cycle regulation. The purpose of this
investigation was to determine if AG induces p21 gene expression in hormone
sensitive (MCF-7) and insensitive (MDA-MB-231) breast cancer cell lines. Cells
grown in steroid stripped medium (SSM) were treated with AG, 17-beta-estradiol
(E2), genistein or cycloheximide (CHX). Northern blot analyses were performed
using human p21Cip1 and 36B4 cDNA probes. Cell lines were transiently transfected
with select mouse p21 CAT reporter constructs, including those lacking a
p53 binding site. Cell cycle analyses was performed by FACScan. The results
revealed that AG induced p21 mRNA expression in MCF-7 and MDA-MB-231
cells (p=0.0004; p≤0.0001, respectively). Neither E2 nor genistein alter p21
mRNA expression. CHX, a protein synthesis inhibitor, did not block p21 mRNA
expression induced by AG, indicating that p21 is induced as an immediate early
gene. AG activated p21 reporter constructs in transfected cells, independent of
p53 binding sites. The cell cycle proliferative phase was significantly decreased
by AG and increased by E2 (p≤0.0001). AG may inhibit breast cancer cell
growth by transcriptional activation of the p21 gene, independent of p53.