The heat shock protein 90 inhibitor induces apoptosis and differentiation of Kasumi-1 and its mechanisms.
- Author:
Wen-juan YU
1
;
Qing RAO
;
Min WANG
;
Zheng TIAN
;
Xiang-rong LIU
;
Dong LIN
;
Jian-xiang WANG
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Benzoquinones; pharmacology; Cell Cycle; drug effects; Cell Differentiation; drug effects; Cell Line, Tumor; Cell Proliferation; drug effects; HSP90 Heat-Shock Proteins; antagonists & inhibitors; Humans; Lactams, Macrocyclic; pharmacology; Proto-Oncogene Proteins c-kit; genetics; metabolism; RNA, Messenger; genetics
- From: Chinese Journal of Hematology 2005;26(12):728-731
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effect of 17-allylamide-17-demethoxygeldanamycin (17AAG), a heat shock protein 90 (HSP90) inhibitor, on the growth, differentiation and apoptosis of leukemic Kasumi-1 cells.
METHODSKasumi-1 cells were treated with 17AAG at different concentrations in suspension culture. Cell proliferation was analysed by MTT assay, expression of myeloid-specific differentiation antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining, agarose gel electrophoresis and flow cytometry. KIT protein was analysed by Western blot and c-kit mRNA by RT-PCR.
RESULTS17AAG treatment caused a dose-dependent inhibition of the cell proliferation with the IC(50) of 0.62 micromol/L. A dose-dependent increase in early apoptosis occurred at 24 hours treatment and in late apoptosis at 48 hours treatment. 17AAG induced a time- and dose-dependent increase in expression of myeloid cell surface protein CD11b and CD15, a progressive decline in S-phase cell fraction and an increase in G(0)/G(1) cells. When Kasumi-1 cells were incubated with 1 micromol/L of 17AAG, KIT protein began to decrease at 2 hours and KIT protein could hardly be detected at 20 hours, but c-kit mRNA was not decreased.
CONCLUSION17AAG treatment of Kasumi-1 cells could lower KIT protein expression, inhibit cell proliferation, induce cell partial differentiation, apoptosis and accumulation in G(0)/G(1) phase.