IDF-11774 Induces Cell Cycle Arrest and Apoptosis by Inhibiting HIF-1α in Gastric Cancer

被引:2
作者
Kim, Won-Ho [1 ]
Kim, Min-Jee [1 ]
Jin, Jun-O [2 ]
Lee, Peter C. W. [1 ]
机构
[1] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Biochem & Mol Biol, Seoul 05505, South Korea
[2] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Microbiol, Seoul 05505, South Korea
基金
新加坡国家研究基金会;
关键词
HIF-1; alpha; HIF-1 alpha inhibitor; gastric cancer; IDF-11774; cell cycle arrest; apoptosis; HIF-1; INHIBITOR; VHL; IDENTIFICATION; PATTERNS; TARGETS; STOMACH; PROTEIN; LW6;
D O I
10.3390/pharmaceutics15122772
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a regulatory factor of intracellular oxygen supersession. The expression or increased activity of HIF-1 alpha is closely related to various human cancers. Previously, IDF-11774 was demonstrated to inhibit HSP70 chaperone activity and suppress the accumulation of HIF-1 alpha. In this study, we aimed to determine the effects of IDF-11774 on gastric cancer cell lines. Treatment with IDF-11774 was found to markedly decrease the proliferation, migration, and invasion of the gastric cancer cell lines. Furthermore, the phosphorylation levels of extracellular signal-regulated kinase 1/2, p38, and Jun N-terminal kinase in the mitogen-activated protein kinase signaling pathways were markedly increased in a dose-dependent manner, ultimately promoting apoptosis via the induction of cell cycle arrest. Our findings indicate that HIF-1 alpha inhibitors are potent drugs for the treatment of gastric cancer.
引用
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页数:12
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