Citrate induces apoptosis of the acute monocytic leukemia U937 cell line through regulation of HIF-1α signaling.
The present study aimed to investigate the anti-tumor effect of citrate on acute monocytic leukemia (AML) and its mechanisms. The apoptosis of the AML cell line, U937, was assessed by MTT and Hoechst staining, the expression of Bcl-2, caspases-3 and -9, hypoxia-inducible factor 1α (HIF‑1α) and its target gene GLUT-1, were assayed by western blotting and the role of HIF‑1α was evaluated through siRNA. The results showed that citrate inhibits the expression of Bcl-2, while it induces the activation of caspases-3 and -9. In addition, citrate induces U937 apoptosis in a dose- and time-dependent manner by regulating the expression of HIF‑1α and its downstream target GLUT-1. The results suggest that citrate performs an anti-acute monocytic leukemia action by targeting HIF‑1α signaling and may be a promising clinical approach.
Department of Hematology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, P.R. Chian.
Xiaowei
X
Xu
Baiwen
B
Li
Peijie
P
Huang
Xinjian
X
Wan
Youwen
Y
Qin
Lili
L
Zhou
Huixia
H
Liu
Haitao
H
Bai
Yanrong
Y
Gao
Chun
C
Wang
Xiangjun
X
Meng
D000925:Anticoagulants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D019343:Citric Acid / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000925:Anticoagulants; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007773:Lactates; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C495677:SLC2A1 protein, human; D019343:Citric Acid; D053148:Caspase 3