Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.
关键词
雷公藤红素/HSDL2/凋亡/基于活性的化学蛋白质组学
Key words
Activity-based protein profiling/Apoptosis/Celastrol/HSDL2
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基金项目
National Key Research and Development Program of China(2020YFA0908000)
National Key Research and Development Program of China(2022YFC2303600)
National Natural Science Foundation of China(81903866)
National Natural Science Foundation of China(82274182)
Central Public Welfare Research Institutes(ZZ13-YQ-105)
Central Public Welfare Research Institutes(ZZ15-YQ-065)
Central Public Welfare Research Institutes(ZZ14-YQ-058)
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