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


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.


CONCLUSIONS
These findings may provide new insights for understanding the mechanisms underlying hypoxia and for designing new therapeutic strategies for acute myeloid leukemia.
Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Yeon-Joo
YJ
Yook
Young-Jin
YJ
Seo
Hyoung Jin
HJ
Kang
Sang-Hyeok
SH
Ko
Hee Young
HY
Shin
Jeong Jin
JJ
Lee
Gajin
G
Jeong
Hyo Seop
HS
Ahn