Premium
NF‐κB pathway is involved in griseofulvin‐induced G2/M arrest and apoptosis in HL‐60 cells
Author(s) -
Uen YihHuei,
Liu DerZen,
Weng MengShih,
Ho YuanSoon,
Lin ShyrYi
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21240
Subject(s) - apoptosis , phosphorylation , griseofulvin , p38 mitogen activated protein kinases , cell cycle checkpoint , cell cycle , chemistry , kinase , mapk/erk pathway , flow cytometry , microbiology and biotechnology , biology , biochemistry , medicine , pathology
Griseofulvin (GF), an oral antifungal agent, has been shown to exert antitumorigenesis effect through G2/M cell cycle arrest in colon cancer cells. But the underlying mechanisms remained obscure. The purpose of this study is to test the cytotoxic effect of GF on HL‐60 and HT‐29 cells and elucidate its underlying molecular pathways. Dose‐dependent and time‐course studies by flow cytometry demonstrated that 30 to 60 µM GF significantly induced G2/M arrest and to a less extend, apoptosis, in HL‐60 cells. In contrast, only G2/M arrest was observed in HT‐29 cells under similar condition. Pretreatment of 30 µM TPCK, a serine protease inhibitor, completely reversed GF‐induced G2/M cell cycle arrest and apoptosis in HL‐60 cells but not in HT‐29 cells. The GF‐induced G2/M arrest in HL‐60 cells is reversible. Using EMSA and super‐shift analysis, we demonstrated that GF stimulated NF‐κB binding activity in HL‐60 cells, which was completely inhibited by pretreatment of TPCK. Treatment of HL‐60 with 30 µM GF activated JNK but not ERK or p38 MAPK and subsequently resulted in phosporylation of Bcl‐2. Pretreatment of TPCK to HL‐60 cells blocked the GF‐induced Bcl‐2 phosphorylation but not JNK activation. Time course study demonstrated that activation of cdc‐2 kinase activity by GF correlated with Bcl‐2 phosphorylation. Taken together, our results suggest that activation of NF‐κB pathway with cdc‐2 activation and phosphorylation of Bcl‐2 might be involved in G2/M cell cycle arrest in HL‐60 cells. J. Cell. Biochem. 101:1165–1175, 2007. © 2007 Wiley‐Liss, Inc.