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Antiproliferative mechanism of a cannabinoid agonist by cell cycle arrest in human gastric cancer cells
Author(s) -
Park Jae Myung,
Xian XiangShu,
Choi MyungGyu,
Park Hyeyeon,
Cho Yu Kyung,
Lee In Seok,
Kim Sang Woo,
Chung InSik
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23041
Subject(s) - cell cycle , cdk inhibitor , cannabinoid receptor , cell cycle checkpoint , cancer cell , agonist , cell growth , cyclin dependent kinase , cannabinoid , cyclin d1 , cancer , chemistry , cancer research , apoptosis , microbiology and biotechnology , biology , receptor , medicine , biochemistry
For gastric cancers, the antineoplastic activity of cannabinoids has been investigated in only a few reports and knowledge regarding the mechanisms involved is limited. We have reported previously that treatment of gastric cancer cells with a cannabinoid agonist significantly decreased cell proliferation and induced apoptosis. Here, we evaluated the effects of cannabinoids on various cellular mediators involved in cell cycle arrest in gastric cancer cells. AGS and MKN‐1 cell lines were used as human gastric cancer cells and WIN 55,212‐2 as a cannabinoid agonist. Cell cycles were analyzed by flow cytometry and western blotting. Treatment with WIN 55,212‐2 arrested the cell cycle in the G0/G1 phase. WIN 55,212‐2 also upregulated phospho‐ERK1/2, induced Kip1/p27 and Cip1/WAF1/p21 expression, decreased cyclin D1 and cyclin E expression, decreased Cdk 2, Cdk 4, and Cdk 6 expression levels, and decreased phospho‐Rb and E2F‐1 expression. ERK inhibitor decreased the proportion of G0/G1 phase which was induced by WIN 55,212‐2. Inhibition of pAKT led to cell cycle arrest in gastric cancer cells. Cell cycle arrest preceded apoptotic response. Thus, this cannabinoid agonist can reduce gastric cancer cell proliferation via G1 phase cell cycle arrest, which is mediated via activation of the MAPK pathway and inhibition of pAKT. J. Cell. Biochem. 112: 1192–1205, 2011. © 2011 Wiley‐Liss, Inc.