Open AccessCitrate induces apoptosis of the acute monocytic leukemia U937 cell line through regulation of HIF-1α signaling
Author(s) -
Xiaowei Xu,
Baiwen Li,
Peijie Huang,
Xinjian Wan,
YaZhen Qin,
Lili Zhou,
Huixia Liu,
Hao Bai,
Yang Gao,
Chun Wang,
Xiangjun Meng
Publication year - 2013
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2013.1702
Subject(s) - u937 cell , apoptosis , cell cycle , monocytic leukemia , thp1 cell line , acute monocytic leukemia , oncogene , cancer research , cell culture , microbiology and biotechnology , molecular medicine , signal transduction , cell , biology , leukemia , immunology , biochemistry , genetics
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.