Apoptosis induced by diacetyldianhydrogalactitol and its mechanism in HL-60 leukemia cells.
- Author:
Jin-nan YANG
1
;
Ju-yuan LIU
;
Hua XU
;
Xiao-li LIU
;
Yu QIN
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Apoptosis; Caspase 3; Caspases; metabolism; Cell Division; drug effects; Dianhydrogalactitol; analogs & derivatives; pharmacology; HL-60 Cells; Humans; Proto-Oncogene Proteins c-bcl-2; metabolism; bcl-X Protein
- From: Acta Pharmaceutica Sinica 2002;37(9):691-695
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigate the apoptosis induced by diacetyldianhydrogalactitol (DADAG) and its mechanism in human HL-60 leukemia cells.
METHODSInhibition of proliferation was measured by MTT assay. DADAG-induced apoptosis in HL-60 cells was observed by electron microscopy, flow cytometry and DNA fragmentation assay. The levels of Bcl-2 family proteins were detected by Western blotting. Caspase-3 activity was determined by ApoAlert CPP32 colorimetric assay kit.
RESULTSDADAG exhibited potent antiproliferative activity and induced apoptosis in HL-60 cells. After treatment with DADAG 8 micrograms.mL-1 for various times, the Bcl-XL protein level decreased in a time-dependent manner, while the Bad protein level was upregulated. The caspase-3 activity increased markedly after treatment with DADAG for 24 h. The apoptotic signals were suppressed by z-VAD.fmk (a general inhibitor of caspases), whereas z-DEVD.fmk, a selective inhibitor of caspase-3, only induced partial reversion of the apoptotic effects.
CONCLUSIONDADAG-induced apoptosis in HL-60 cells required caspase-3 activation and caspase-3 activation was related with Bcl-2 family members.
