IDF-11774 Induces Cell Cycle Arrest and Apoptosis by Inhibiting HIF-1α in Gastric Cancer.
Won-Ho KimMin-Jee KimJun-O JinPeter Chang-Whan LeePublished in: Pharmaceutics (2023)
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.
Keyphrases
- cell cycle arrest
- pi k akt
- cell death
- signaling pathway
- endothelial cells
- protein kinase
- tyrosine kinase
- transcription factor
- poor prognosis
- heat shock protein
- cell proliferation
- endoplasmic reticulum stress
- epithelial mesenchymal transition
- combination therapy
- heat shock
- anti inflammatory
- heat stress
- endoplasmic reticulum