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

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.

• Authors: Hae Young Park, Min Kyoung Kim, Sang-Ik Moon, Youl-Hee Cho, Chul-Hoon Lee
• Journal: Cancer science (Cancer Sci) Vol. 97 Issue 5 Pg. 430-6 (May 2006) ISSN: 1347-9032 [Print] England
• PMID: 16630142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• MCS-C2
• Tumor Suppressor Protein p53
• Serine
• Cyclin-Dependent Kinases
• Toyocamycin

Topics

• Antineoplastic Agents (metabolism, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Cyclin-Dependent Kinases (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Humans
• Male
• Phosphorylation
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Serine (metabolism)
• Signal Transduction (drug effects)
• Toyocamycin (analogs & derivatives, metabolism, pharmacology, therapeutic use)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (metabolism)
• Up-Regulation