Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells

Jifeng Wang, Baobing Zhao, Wei Zhang, Xuan Wu, Ruoyu Wang, Yaojian Huang, Dong Chen, Kum Park, Bart C Weimer, Yuemao Shen

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forests. It contains an oxygen-bridged cyclooctadiene core and an α,β-unsaturated δ-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.

Original languageEnglish (US)
Pages (from-to)7054-7058
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number23
DOIs
StatePublished - Dec 1 2010

Keywords

  • Apoptosis
  • G2/M arrest
  • MAPK
  • Mycoepoxydiene
  • Polyketide

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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