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KMID : 0366220100450030158
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Korean Journal of Hematology
2010 Volume.45 No. 3 p.158 ~ p.163
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Induction of hypoxia-inducible factor-1a inhibits drug-induced apoptosis in the human leukemic cell line HL-60
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Yook Yeon-Joo
Seo Young-Jin
Kang Hyoung-Jin
Ko Sang-Hyeok
Shin Hee-Young
Lee Jeong-Jin
Jeong Ga-Jin
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Abstract
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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-1a 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.
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KEYWORD
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Hypoxia, Arsenic trioxide, HIF-1a, Cobalt chloride, Bax, HSP70
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