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Widdrol induces cell cycle arrest, associated with MCM down-regulation, in human colon adenocarcinoma cells.

Abstract
Widdrol, an odorous compound extracted from Juniperus chinensis, has been shown to inhibit the in vitro growth of in human cancer cells. This study was conducted on cultured human colon adenocarcinoma HT29 cells to elucidate the possible mechanisms by which widdrol exerts its anti-proliferative activity, which until now has remained poorly understood. It was found that widdrol induces accumulation of sub-G1 phase and arrests in the G1 phase of the cell cycle. Induction of G1 arrest by widdrol was correlated with induction of Chk2, p53 phosphorylation and CDK inhibitor p21 expression as well as inhibition of cyclin E, cyclin-dependent kinase (CDK2) and retinoblastoma protein (pRB). Moreover, mini-chromosome maintenance (MCM) proteins were markedly down-regulated in HT29 cells treated with widdrol. Altogether, these results show widdrol possesses potential anti-cancer activity against colon adenocarcinoma cells by inhibiting their proliferation and inducing cell cycle G1 arrest.
AuthorsHyun Ju Kwon, Yun Kyung Hong, Cheol Park, Yung Hyun Choi, Hee Jung Yun, Eun Woo Lee, Byung Woo Kim
JournalCancer letters (Cancer Lett) Vol. 290 Issue 1 Pg. 96-103 (Apr 01 2010) ISSN: 1872-7980 [Electronic] Ireland
PMID19828235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright2009 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Benzocycloheptenes
  • Cell Cycle Proteins
  • Minichromosome Maintenance 1 Protein
  • Nuclear Proteins
  • Plant Extracts
  • widdrol
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2
Topics
  • Adenocarcinoma (metabolism)
  • Benzocycloheptenes (pharmacology)
  • Blotting, Western
  • Cell Cycle (drug effects)
  • Cell Cycle Proteins (drug effects, metabolism)
  • Cell Separation
  • Colonic Neoplasms (metabolism)
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression (drug effects)
  • Gene Expression Profiling
  • HT29 Cells
  • Humans
  • Immunoprecipitation
  • Juniperus (chemistry)
  • Minichromosome Maintenance 1 Protein (drug effects, metabolism)
  • Minichromosome Maintenance Complex Component 2
  • Nuclear Proteins (drug effects, metabolism)
  • Oligonucleotide Array Sequence Analysis
  • Plant Extracts (pharmacology)
  • Reverse Transcriptase Polymerase Chain Reaction

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