題名:NF-B pathway is involved in griseofulvin-induced G2/M arrest and apoptosis in HL60 cells
作者:何元順
Yih-Huei Uen; Der-Zen Liu; Meng-Shih Weng; Yuan-Soon Ho;
Shyr-Yi Lin;
貢獻者:醫學檢驗暨生物技術學系 上傳時間:2009-08-25T02:38:45Z
摘要:Griseofulvin (GF), an oral antifungal agent, has been shown to exert antitumorigenesis effect through
G2/Mcell 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.
Dosedependent
and time-course studies byflowcytometry demonstrated that 30 to 60 mMGF significantly inducedG2/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 mM 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-kB binding activity in HL-60 cells, which was
completely inhibited by pretreatment of TPCK. Treatment of HL-60 with 30 mMGF activated JNK but not ERK or
p38MAPK
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-kB 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.
