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Induction of hypoxia-inducible factor-1α inhibits drug-induced apoptosis in the human leukemic cell line HL-60.
- Source :
-
The Korean journal of hematology [Korean J Hematol] 2010 Sep; Vol. 45 (3), pp. 158-63. Date of Electronic Publication: 2010 Sep 30. - Publication Year :
- 2010
-
Abstract
- Background: Leukemic cells originate from hypoxic bone marrow, which protects them from anti-cancer drugs. Although many factors that cause drug resistance in leukemic cells have been studied, the effect of hypoxia on drug-induced apoptosis is still poorly understood.<br />Methods: In this study, we examined the effect of hypoxia on anti-leukemic drug resistance in leukemic cell lines treated with cobalt chloride (CoCl(2)), a hypoxia-mimetic agent. Cellular proliferation was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry analysis and western blots were performed to investigate apoptosis-related proteins.<br />Results: Unlike its previously known apoptotic effect, the expression of HIF-1α increased the survival rate of human promyelocytic leukemia HL-60 cells when these cells were exposed to anti-leukemic drugs; these effects were mediated by heat-shock protein HSP70 and the pro-apoptotic protein Bax.<br />Conclusion: These findings may provide new insights for understanding the mechanisms underlying hypoxia and for designing new therapeutic strategies for acute myeloid leukemia.
Details
- Language :
- English
- ISSN :
- 2092-9129
- Volume :
- 45
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Korean journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 21120203
- Full Text :
- https://doi.org/10.5045/kjh.2010.45.3.158