[Apoptosis induced by diacetyldianhydrogalactitol and its mechanism in HL-60 leukemia cells].

Abstract

AIM:

To investigate the apoptosis induced by diacetyldianhydrogalactitol (DADAG) and its mechanism in human HL-60 leukemia cells.

METHODS:

Inhibition 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.

RESULTS:

DADAG 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.

CONCLUSION:

DADAG-induced apoptosis in HL-60 cells required caspase-3 activation and caspase-3 activation was related with Bcl-2 family members.

• Authors: Jin-nan Yang, Ju-yuan Liu, Hua Xu, Xiao-li Liu, Yu Qin
• Journal: Yao xue xue bao = Acta pharmaceutica Sinica (Yao Xue Xue Bao) Vol. 37 Issue 9 Pg. 691-5 (Sep 2002) ISSN: 0513-4870 [Print] China
• PMID: 12567892 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antineoplastic Agents
• BCL2L1 protein, human
• Proto-Oncogene Proteins c-bcl-2
• bcl-X Protein
• Dianhydrogalactitol
• dianhydro-3,4-diacetylgalactitol
• CASP3 protein, human
• Caspase 3
• Caspases

Topics

• 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