YC-1 suppresses constitutive nuclear factor-κB activation and induces apoptosis in human prostate cancer cells

摘要: Although the indazole compound, YC-1, is reported to exert anticancer activities in several cancer cell types, its target and mechanism of action have not been well explored. The objectives this study were ascertain whether YC-1 directly induces apoptosis prostate cells explore mechanism(s) whereby causes death. Hormone-refractory metastatic human PC-3 selected for study. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay indicated that suppresses growth a concentration-dependent time-dependent manner. Apoptosis was determined using 4′,6-diamidino-2-phenylindole staining, cycle progression examined by FACScan flow cytometry. treatment showed chromatin condensation increased percentage hypodiploid sub-G-G1 phase, indicative apoptosis. Additionally, exposure found induce activation caspase-3 cleavage poly(ADP-ribose) polymerase. Translocation nuclear factor-κB (NF-κB) immunofluorescent staining ELISA, respectively. results abolished constitutive translocation NF-κB/p65. Furthermore, inhibition inhibitor κBα (IκBα) phosphorylation accumulation IκBα observed. antitumor effects evaluated measuring tumor xenografts YC-1-treated severe combined immunodeficient mice. volumes tumors produced mice observed decline significantly after with compared vehicle controls. We concluded include induction suppression NF-κB activation. Given these unique actions, further investigations against hormone-refractory are warranted.