HY251, a novel cell cycle inhibitor isolated from Aralia continentalis, induces G(1) phase arrest via p53-dependent pathway in HeLa cells

Abstract

This study was aimed to elucidate the novel structure of HY251 isolated from the roots of Aralia continentalis and to evaluate its detailed inhibition mechanisms on cell cycle progression in HeLa cells. The structure of HY251 was elucidated based on the interpretation of the NMR spectra, as 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta[alpha]indene-3,3a, 7a,8a-tetraol. The flow cytometric analysis revealed an appreciable G(1) phase arrest in HeLa cells treated with 100 mu M of HY251. This HY251-induced G1 phase arrest is associated with decreased expression of cyclin D3 and up-regulation of p21(CIP1) and p27(KIP1), via p53 phosphorylation at Ser-15 by transcriptional up-regulation of ATM, which resulted in increased hypophosphorylated pRb in HeLa cells. (C) 2008 Elsevier Ltd. All rights reserved.