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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.
AuthorsHae Young Park, Min Kyoung Kim, Sang-Ik Moon, Youl-Hee Cho, Chul-Hoon Lee
JournalCancer science (Cancer Sci) Vol. 97 Issue 5 Pg. 430-6 (May 2006) ISSN: 1347-9032 [Print] England
PMID16630142 (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

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