Beta-catenin mediates the apoptosis induction effect of celastrol in HT29 cells

We evaluated the apoptosis induction effects of celastrol in human colorectal cancer cell line HT29 in WNT/beta-catenin pathway. HT29 cells were treated with various concentrations (10–100 μM) for 24 h, MTT assay was performed to examine the effect of celastrol on growth inhibition of HT29 cells. Beta-catenin siRNA was used for transfection of cells. Cell apoptosis was detected through both DNA laddering analysis and Tdt-mediated dUTP nick end labeling (TUNEL) assay. Western blot analysis and real-time reverse transcription polymerase chain reaction technologies were applied to assess the expression level of c-Myc, Bax, and Bcl-2 in HT29 cells. Treatment of HT29 cells with celastrol resulted in a growth inhibition effect, and the IC50 value was 56 μM. Celastrol induced HT29 cells apoptosis, and increased the nuclear translocation of beta-catenin. Apoptosis induction effects of celastrol were significantly attenuated by beta-catenin siRNA transfection. Beta-catenin siRNA markedly increased mRNA and protein levels of c-Myc compared with control siRNA. Beta-catenin siRNA significantly inhibited the expression of Bax and Bcl-2 in celastrol-treated HT29 cells. Beta-catenin mediates the apoptosis induction effects of celastrol in HT29 cells.