Bardoxolone methyl induces apoptosis and autophagy and inhibits epithelial-to-mesenchymal transition and stemness in esophageal squamous cancer cells.

Drug Design, Development and Therapy
Yan-Yang WangShu-Feng Zhou

Abstract

Natural and synthetic triterpenoids have been shown to kill cancer cells via multiple mechanisms. The therapeutic effect and underlying mechanism of the synthetic triterpenoid bardoxolone methyl (C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; CDDO-Me) on esophageal cancer are unclear. Herein, we aimed to investigate the anticancer effects and underlying mechanisms of CDDO-Me in human esophageal squamous cell carcinoma (ESCC) cells. Our study showed that CDDO-Me suppressed the proliferation and arrested cells in G2/M phase, and induced apoptosis in human ESCC Ec109 and KYSE70 cells. The G2/M arrest was accompanied with upregulated p21Waf1/Cip1 and p53 expression. CDDO-Me significantly decreased B-cell lymphoma-extra large (Bcl-xl), B-cell lymphoma 2 (Bcl-2), cleaved caspase-9, and cleaved poly ADP ribose polymerase (PARP) levels but increased the expression level of Bcl-2-associated X (Bax). Furthermore, CDDO-Me induced autophagy in both Ec109 and KYSE70 cells via suppression of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. There were interactions between the autophagic and apoptotic pathways in Ec109 and KYSE70 cells subject to CDDO-Me treatme...Continue Reading

Citations

Feb 6, 2020·The Journal of Pharmacology and Experimental Therapeutics·Liang ZhouDesheng Lu
Nov 20, 2019·Medicinal Research Reviews·Tuhina KhanGiuseppe Campiani
Dec 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Andrey V MarkovMarina A Zenkova
Nov 16, 2018·ACS Medicinal Chemistry Letters·Lian-Fang YangWen-Wei Qiu

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Methods Mentioned

BETA
xenograft
biopsies
Assay
transfection
flow cytometry
confocal microscopy
electrophoresis
ubiquitination
environmental stress
nuclear translocation

Software Mentioned

GraphPad
Prism
ImageJ

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