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

Author:

Kim Won-Ho1,Kim Min-Jee1ORCID,Jin Jun-O2ORCID,Lee Peter C. W.1ORCID

Affiliation:

1. Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

2. Department of Microbiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

Abstract

Hypoxia-inducible factor-1 alpha (HIF-1α) is a regulatory factor of intracellular oxygen supersession. The expression or increased activity of HIF-1α is closely related to various human cancers. Previously, IDF-11774 was demonstrated to inhibit HSP70 chaperone activity and suppress the accumulation of HIF-1α. 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-1α inhibitors are potent drugs for the treatment of gastric cancer.

Funder

National Research Foundation of Korea

Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea

Publisher

MDPI AG

Subject

Pharmaceutical Science

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