Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells.
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.
Wang
Jifeng
J
Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Zhao
Baobing
B
Zhang
Wei
W
Wu
Xuan
X
Wang
Ruoyu
R
Huang
Yaojian
Y
Chen
Dong
D
Park
Kum
K
Weimer
Bart C
BC
Shen
Yuemao
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D005658:Fungi / Q000737:chemistry; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases; D011753:Pyrones / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D011753:Pyrones; C476085:mycoepoxydiene; D020928:Mitogen-Activated Protein Kinases