期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 20, 期 23, 页码 7054-7058出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2010.09.105
关键词
Mycoepoxydiene; Polyketide; G2/M arrest; MAPK; Apoptosis
资金
- NSFC [90913024]
- 863 Program [2007AA091503, 2006AA09Z410]
- 973 Program [2010CB83 3802]
- National Science Fund for Distinguished Young Scholars [30325044]
- United States Department of Agriculture [2008-34526-19199]
- NIFA [583611, 2008-34526-19199] Funding Source: Federal RePORTER
Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forests. It contains an oxygen-bridged cyclooctadiene core and an alpha,beta-unsaturated delta-lactone moiety. MED induced the reorganization of cytoskeleton in actively growing HeLa cells by promoting formation of actin stress fiber and inhibiting polymerization of tubulin. MED could induce cell cycle arrest at G2/M in HeLa cells. MED-associated apoptosis was characterized by the formation of fragmented nuclei, PARP cleavage, cytochrome c release, activation of caspase-3, and an increased proportion of sub-G1 cells. Additionally, MED activated MAPK pathways. Interestingly, the time of JNK, p38, and Bcl-2 activation did not correlate with the release of cytochrome c. This study is the first report demonstrating the action mechanism of MED against tumor cell growth. These results provide the potential of MED as a novel low toxic antitumor agent. (C) 2010 Elsevier Ltd. All rights reserved.
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