[Betaine induces apoptosis of C4-2B prostate cancer cells via inhibiting PI3K/AKT/NF-κB signaling pathway].

Objective To investigate the inhibitory effect of betaine (BET) on the proliferation of C4-2B prostate cancer cells and its possible mechanism. Methods C4-2B cells were treated with 0, 100, 200, 400, 600, 800 mmol/L BET. CCK-8 assay was used to assess the cell proliferation, plate cloning formation assay to detect clone formation ability and flow cytometry to evaluate cell apoptosis, and the cell morphological alteration was observed by microscopy. The protein expression of BAX, Bcl2, cleaved caspase 3 (c-caspase-3), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and NF-κB p65 were detected by Western blotting, and the changes of BAX, Bcl2, c-caspase-3, and NF-κB p65 proteins were further verified after the cells were treated with NF-κB pathway inhibitor BAY11-7082. Results BET inhibited the proliferation of C4-2B cells in a dose-dependent manner. The 50% inhibitory concentration (IC) was 422.7 mmol/L after the cells were treated with BET for 48 hours. Compared with the control group (0 mmol/L BET treatment), the proliferation of C4-2B cells was inhibited along with morphological changes, decreased clone formation ability and increased apoptosis rate in 200, 300, 400 mmol/L BET treated groups. Meanwhile, the protein expression of BAX and c-caspase-3 were up-regulated and Bcl2, PI3K, AKT and NF-κB p65 were down-regulated in 300, 400 mmol/L BET groups as compared with the control group. After BAY11-7082 treatment alone, Bcl2, BAX, c-caspase-3, NF-κB p65 protein expression trend was consistent with that of the 300 mmol/L BET treated group, and Bcl2, NF-κB p65 protein expression levels were lower and BAX and c-caspase-3 protein expression levels were higher in BET combined with BAY11-7082 treated group. Conclusion BET can inhibit C4-2B cell proliferation and induce its apoptosis by blocking PI3K/AKT/NF-κB signaling pathway.