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The p53 pathway is synergized by p38 MAPK signaling to mediate 11,11′‐dideoxyverticillin‐induced G 2 /M arrest
Author(s) -
Chen Yi,
Miao Ze-Hong,
Zhao Wei-Min,
Ding Jian
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.05.053
Subject(s) - p38 mitogen activated protein kinases , cell cycle checkpoint , mapk/erk pathway , biology , kinase , phosphorylation , in vitro , cell cycle , in vivo , microbiology and biotechnology , signal transduction , cancer research , cell , biochemistry , genetics
The phytochemical 11,11′‐dideoxyverticillin, derived from the fungus Shiraia bambusicola , has been shown to possess potent anticancer activity in vitro and in vivo. Here, we investigated the effect of 11,11′‐dideoxyverticillin on cell cycle progression, and explored the potential mechanisms for this effect. A concentration‐ and time‐dependent cell cycle blockade at G 2 /M phase was observed in human colon cancer cells (HCT‐116) following 11,11′‐dideoxyverticillin treatment and was associated with marked increases in levels of p53, phospho‐p53(ser20) and phospho‐Chk2(Thr 68). When wild type p53 expression was specifically inhibited by RNA interference, HCT‐116 cells treated with 11,11′‐dideoxyverticillin failed to arrest in G 2 /M and did not show increased phospho‐Chk2(Thr 68). On the other hand, 11,11′‐dideoxyverticillin treatment also elicited p38 MAP kinase activity and expression of phospho‐p38 MAPK. Treatment with a specific p38 MAPK inhibitor (SB203580) successfully inhibited p38 MAPK and delayed the onset of G 2 /M arrest induced by 0.5 μM 11,11′‐dideoxyverticillin after approximately 6 h, but did not abolish the induction of G 2 /M arrest. Additionally, SB203580 did not alter the levels of p53, phospho‐p53 (ser20), or phospho‐Chk2 (Thr68) proteins in 11,11′‐dideoxyverticillin‐treated cells. Together, these findings indicate that p53‐mediated phosphorylation of Chk2 maybe plays a vital role in 11,11′‐dideoxyverticillin‐induced G 2 /M arrest, and that p38 MAPK might accelerate this progression. Our work suggests a new possibility of interactions among p53, Chk2 and p38 MAPK signaling in G 2 /M arrest.