Cell cycle arrest and apoptotic induction in LNCaP cells by MCS-C2, novel cyclin-dependent kinase inhibitor, through p53/p21WAF1/CIP1 pathway

Cancer Science
Hae Young ParkChul-Hoon Lee

Abstract

The purpose of the present study was to investigate the mechanisms involved in the antiproliferative and apoptotic effects of MCS-C2, a novel analog of the pyrrolo[2,3-d]pyrimidine nucleoside toyocamycin and sangivamycin, in human prostate cancer LNCaP cells. MCS-C2, a selective inhibitor of cyclin-dependent kinase, was found to inhibit cell growth in a time- and dose-dependent manner, and inhibit cell cycle progression by inducing the arrest of the G1 phase and apoptosis in LNCaP cells. When treated with 3 microM MCS-C2, inhibited proliferation associated with apoptotic induction was found in the LNCaP cells in a concentration and time-dependent manner, and nuclear DAPI staining revealed the typical nuclear features of apoptosis. Furthermore, MCS-C2 induced cell cycle arrest in the G1 phase through the upregulated phosphorylation of the p53 protein at Ser-15 and activation of its downstream target gene p21WAF1/CIP1. Accordingly, these results suggest that MCS-C2 inhibits the proliferation of LNCaP cells by way of G1-phase arrest and apoptosis in association with the regulation of multiple molecules in the cell cycle progression.

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Citations

Nov 30, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xia ZhaoGuosheng Jiang
Jun 27, 2013·MBio·Anand SrinivasanAnand K Ramasubramanian
Apr 18, 2007·Molecular Cancer·Dimitri G TrembathGregory J Riggins
Jun 8, 2013·Pharmacological Reports : PR·Chunyan YuJing Liu

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