Induction of hypoxia-inducible factor-1α inhibits drug-induced apoptosis in the human leukemic cell line HL-60

• Published in: Korean journal of hematology Vol. 45; no. 3; pp. 158 - 163
• Main Authors: Yook, Yeon-Joo, Seo, Young-Jin, Kang, Hyoung Jin, Ko, Sang-Hyeok, Shin, Hee Young, Lee, Jeong Jin, Jeong, Gajin, Ahn, Hyo Seop
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society of Hematology; Korean Society of Blood and Marrow Transplantation; Korean Society of Pediatric Hematology-Oncology; Korean Society on Thrombosis and Hemostasis 01.09.2010
• Subjects: Original; Bax; Arsenic trioxide; Hypoxia; HIF-1α; HSP70; Cobalt chloride
• ISSN: 1738-7949; 2092-9129
• DOI: 10.5045/kjh.2010.45.3.158

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. 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. 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. These findings may provide new insights for understanding the mechanisms underlying hypoxia and for designing new therapeutic strategies for acute myeloid leukemia.