Celastrol promotes apoptosis of breast cancer MDA-MB-231 cells by targeting HSDL2
Li Liu, Yanqing Liu, Shujie Zhang, Junzhe Zhang, Yuqing Meng, Dandan Liu, Liwei Gu, Ying Zhang, Liting Xu, Ziyue Zhang, Minghong Zhao, Yin‐Kwan Wong, Qixin Wang, Yongping Zhu, Jigang Wang
Abstract
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.