title: The antipsychotic drug pimozide inhibits cell growth in prostate cancer through suppression of STAT3 activation.
abstract: Currently, drug discovery and development for clinical treatment of prostate cancer has received increased attention, specifically the STAT3 inhibitor. Our previous study reported that the neuroleptic drug pimozide had antitumor activity against hepatocellular carcinoma cells or stem-like cells through suppressing the STAT3 activity. In the present study we demonstrate that pimozide inhibits cell growth and cellular STAT3 activation in prostate cancer cells. Our results showed that pimozide inhibited prostate cancer cell proliferation in a dose- and time-dependent manner by inducing G1 phase cell cycle arrest, downregulated the ability of colony formation and sphere forming, as well as suppressed cells migration in both DU145 and LNCaP cells. Surprisingly, pimozide reduced the basal expression of phosphorylation STAT3 at tyrosine 705 and reversed the expression of phosphorylation of STAT3 induced by IL-6 addition, suggesting that pimozide can suppress cellular STAT3 activation. Thus, the antipsychotic agent pimozide may be a potential and novel therapeutic for patients with advanced prostate cancer.
authors.affiliation: Department of Orthopedics, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Urology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, P.R. China.
authors.forename: Ming-Kun
authors.initials: MK
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Hao-Tao
authors.initials: HT
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zhong
authors.affiliation: Vaccine Research Institute of Sun Yat-sen University, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Cai
authors.affiliation: Vaccine Research Institute of Sun Yat-sen University, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Guan-Zhong
authors.initials: GZ
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Vaccine Research Institute of Sun Yat-sen University, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D010868:Pimozide / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D014150:Antipsychotic Agents; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D010868:Pimozide