Induction of hypoxia-inducible factor-1alpha inhibits drug-induced apoptosis in the human leukemic cell line HL-60.
10.5045/kjh.2010.45.3.158
- Author:
Yeon Joo YOOK
1
;
Young Jin SEO
;
Hyoung Jin KANG
;
Sang Hyeok KO
;
Hee Young SHIN
;
Jeong Jin LEE
;
Gajin JEONG
;
Hyo Seop AHN
Author Information
1. Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. hsahn@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Hypoxia;
Arsenic trioxide;
HIF-1alpha;
Cobalt chloride;
Bax;
HSP70
- MeSH:
Anoxia;
Apoptosis;
Arsenicals;
Blotting, Western;
Bone Marrow;
Cell Line;
Cell Proliferation;
Cobalt;
Drug Resistance;
Flow Cytometry;
Heat-Shock Proteins;
HL-60 Cells;
Humans;
Leukemia;
Leukemia, Myeloid, Acute;
Oxides;
Proteins;
Survival Rate
- From:Korean Journal of Hematology
2010;45(3):158-163
- CountryRepublic of Korea
- Language:English
-
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. METHODS: In this study, we examined the effect of hypoxia on anti-leukemic drug resistance in leukemic cell lines treated with cobalt chloride (CoCl2), 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. RESULTS: Unlike its previously known apoptotic effect, the expression of HIF-1alpha 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. CONCLUSION: These findings may provide new insights for understanding the mechanisms underlying hypoxia and for designing new therapeutic strategies for acute myeloid leukemia.
