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

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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

Fingerprint

Polyketides
G2 Phase
Cell Cycle Checkpoints
HeLa Cells
Cell Division
Cells
Apoptosis
Cytochromes c
Chemical activation
G2 Phase Cell Cycle Checkpoints
Stress Fibers
Wetlands
Poisons
Cell growth
Lactones
Tubulin
mycoepoxydiene
Fungi
Cytoskeleton
Caspase 3

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

Cite this

Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells. / Wang, Jifeng; Zhao, Baobing; Zhang, Wei; Wu, Xuan; Wang, Ruoyu; Huang, Yaojian; Chen, Dong; Park, Kum; Weimer, Bart C; Shen, Yuemao.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 23, 01.12.2010, p. 7054-7058.

Research output: Contribution to journalArticle

Wang, Jifeng ; Zhao, Baobing ; Zhang, Wei ; Wu, Xuan ; Wang, Ruoyu ; Huang, Yaojian ; Chen, Dong ; Park, Kum ; Weimer, Bart C ; Shen, Yuemao. / Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 23. pp. 7054-7058.
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AU - Wang, Ruoyu

AU - Huang, Yaojian

AU - Chen, Dong

AU - Park, Kum

AU - Weimer, Bart C

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