Casein kinase 2 inhibitor reduces androgen receptor function and cell proliferation in prostate cancer cells

Abstract

Objective To investigate the role of casein kinase 2 (CK2) selective inhibitor tribromoisocyanuric acid (TBCA) in androgen receptor (AR) transactivation,cell proliferation and viability in prostate cancer cell lines,and explore a new chemotherapy for prostate cancer.Methods Prostate cancer cell lines were prepared.With TBCA treatment,Alamar-blue assay was performed to assess cell proliferation and viability in C4-2 cells and flow cytometry was performed for cell cycle analysis in C4-2 and 22Rvl cells; while immunofluorescence staining was performed to determine AR nuclear translocationin in PC-3/AR cells with R1881 pretreatment,and luciferase gene reporter assay was performed to determine AR transactivation in LNCaP cells; Reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the mRNA level of prostate specific antigen (PSA).Results With TBCA treatment,Alamar-blue reading decreased in a dose-dependent manner,and the 50％ inhibitory concentration ( IC50 ) was around 25 mol/L.Significant G2/M arrest was detected in C4-2 and 22Rvl cells.R1881-induced AR nuclear localization was reduced significantly ( P ＜ 0.01 ).R1881 -stimulated ARE-LUC reporter activity in LNCaP cells decreased with reduced level of PSA mRNA,which was an AR endogenous target( P ＜ 0.05 ).Conclusion The selective CK2 inhibitor TBCA can dramatically inhibite cell proliferation and cause a G2/M phase arrest in prostate cancer cells. Key words: Casein kinase 2; Prostate cancer; . Androgen receptor; Cell proliferation; Tribromoisocyanuric acid