【Objective】 To investigate the mechanism of celastrol degradating HER2 protein and inducing cell apoptosis in MDA-MB-453 cells. 【Methods】 The cytotoxicity of celastrol to MDA-MB-453 cells was measured by MTT assay. Apoptotic morphology was observed after Hoechst 33258 staining. Sub-G1 DNA peak was analyzed by flow cytometry to quantify the degree of apoptosis. Changes of apoptotic related proteins were analyzed by Western blot. Subcellular distribution of HER2 was observed under fluorescence microscopy by immunofluorescence assay. 【Results】 Celastrol exhibited potent cytotoxicity in HER2-overexpressing MDA-MB-453 cells

and IC50 was (5.22 ± 0.29) μmol/L. After MDA-MB-453 cells were treated with different concentrations of celastrol for 24 h

typical apoptotic bodies

increasing sub-G1 DNA peak and activation of Caspase-3 and Parp were detected in a dose-dependent manner. It was noteworthy that immunofluorescence study with anti-HER2 antibody showed that celastrol disturbed the subcellular distribution of HER2

with decreased location in the plasma membrane. 【Conclusion】 Celastrol induced MDA-MB-453 cancer cells apoptosis in a dose-dependent manner. Subcellular redistribution of HER2 maybe involved in HER2 protein degradation by celastrol.