Parthenolide suppresses hypoxia-inducible factor-1α signaling and hypoxia induced epithelial-mesenchymal transition in colorectal cancer

International Journal of Oncology
Se Lim KimSang Wook Kim

Abstract

Activation of hypoxia-inducible factor 1α (HIF‑1α) is frequently observed in solid tumors and it has been associated with various pathophysiological processes, including epithelial‑mesenchymal transition (EMT). Previously, we reported that parthenolide (PT), an inhibitor of nuclear factor-κB (NF-κB), is a promising anticancer agent because it promotes apoptosis of human colorectal cancer (CRC). Here, we investigated a new molecular mechanism by which PT acts on HIF‑1α and hypoxia contributing to EMT by NF‑κB inhibition. Cell viability, DNA binding activity, vascular cell tube formation and cell motility were studied after treatment of PT in hypoxic or normoxic condition. Moreover, effects of PT on hypoxia signaling and hypoxia-induced EMT signaling were investigated. We also examined the inhibitory effect of PT on CRC progression in xenografts. We demonstrated that PT markedly inhibits hypoxia dependent HIF‑1α activity and angiogenesis by preventing NF-κB activation. We also report that PT decreases the level of proteins associated with glucose metabolism, angiogenesis, development and survival that are regulated by HIF‑1α. Furthermore, we verified that PT protects the morphological change from epithelial to mesenchymal state, ...Continue Reading

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Citations

Nov 26, 2019·Natural Product Reports·Robert R A FreundHans-Dieter Arndt
Nov 6, 2018·Molecular Medicine Reports·Huan ZhouMing-Jun Sun
Nov 15, 2019·Journal of Cancer Research and Clinical Oncology·Devarajan NaliniGanesan Senthil Kumar
Jan 27, 2021·International Journal of Molecular Sciences·Younghoon KimTaebo Sim
Feb 26, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shuzhen SunYapo Xu
Dec 9, 2020·Journal of Medicinal Chemistry·Yulin Ren, A Douglas Kinghorn

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