Effect of celastrol on growth inhibition of prostate cancer cells through the regulation of hERG channel in vitro.

Abstract

Objective. To explore the antiprostate cancer effects of Celastrol on prostate cancer cells' proliferation, apoptosis, and cell cycle distribution, as well as the correlation to the regulation of hERG. Methods. DU145 cells were treated with various concentrations of Celastrol (0.25–16.0 μmol/L) for 0–72 hours. MTT assay was used to evaluate the inhibition effect of Celastrol on the growth of DU145 cells. Cell apoptosis was detected through both Annexin-V FITC/PI double-labeled cytometry and Hoechst 33258. Cell cycle regulation was examined by a propidium iodide method. Western blot and RT-PCR technologies were applied to assess the expression level of hERG in DU145 cells. Results. Celastrol presented striking growth inhibition and apoptosis induction potency on DU145 cells in vitro in a time- and dose-dependent manner. The IC50 value of Celastrol for 24 hours was 2.349 ± 0.213 μmol/L. Moreover, Celastrol induced DU145 cell apoptosis in a cell cycle-dependent manner, which means Celastrol could arrest DU145 cells in G0/G1 phase; accordingly, cells in S phase decreased gradually and no obvious changes were found in G2/M phase cells. Through transmission electron microscope, apoptotic bodies containing nuclear fragments were found in Celastrol-treated DU145 cells. Overexpression of hERG channel was found in DU145 cells, while Celastrol could downregulate it at both protein and mRNA level in a dose-dependent manner (P < 0.01). Conclusions. Celastrol exhibits its antiprostate cancer effects partially through the downregulation of the expression level of hERG channel in DU145 cells, suggesting that Celastrol may be a potential agent against prostate cancer with a mechanism of blocking the hERG channel.