title: Targeting fatty acid synthase with ASC-J9 suppresses proliferation and invasion of prostate cancer cells.
abstract: Fatty acid synthase (FASN) is the key enzyme for the control of fatty acid synthesis that contributes significantly to the prostate cancer (PCa) progression. It was reported that androgens were able to induce FASN expression in PCa, and addition of the anti-androgen Casodex might suppress the androgen-induced FASN expression. However, here we found androgen-deprivation-therapy (ADT) with anti-androgens Bicalutamide (Casodex) or Enzalutamide (MDV3100) had little effect to suppress FASN expression and FASN-mediated cell growth and invasion during the castration resistant stage when the androgen concentration is 1 nM DHT (dihydrotestosterone). In contrast, the newly developed androgen receptor (AR) degradation enhancer ASC-J9®suppressed FASN expression and FASN-mediated cell growth and invasion in various PCa cell lines at 1 nM DHT. Mechanism dissection found ASC-J9®could suppress significantly the FASN expression and FASN-mediated PCa progression via the AR-dependent pathway involving AR→SREBP-1→FASN signaling in AR-positive C4-2 and LNCaP cells and via the AR-independent pathway involving the modulation of PI3K/AKT→SREBP-1→FASN signaling in AR-negative PC-3 and DU145 cells. Together, these results suggest that FASN is one of the important mechanism why the current ADT eventually fails. ASC-J9®might represent a new potential therapeutic approach to suppress FASN-mediated PCa progression via both AR-dependent and AR-independent pathways during the castration resistant stage of PCa. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, University of Tianjin Medical, Tianjin, China.|Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, New York.
authors.forename: Simeng
authors.initials: S
authors.lastname: Wen
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, University of Tianjin Medical, Tianjin, China.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, New York.
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, New York.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, University of Tianjin Medical, Tianjin, China.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Shang
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, University of Tianjin Medical, Tianjin, China.
authors.forename: Hengheng
authors.initials: H
authors.lastname: Gao
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, University of Tianjin Medical, Tianjin, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, New York.
authors.forename: Fuju
authors.initials: F
authors.lastname: Chou
authors.affiliation: Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, New York.|Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D054890:Fatty Acid Synthase, Type I / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D003474:Curcumin; D054890:Fatty Acid Synthase, Type I; D009570:Nitriles; D010669:Phenylthiohydantoin; C471106:ASC-J9 compound; C540278:enzalutamide; C518729:FASN protein, human
keywords: ASC-J9®; androgen deprivation therapy; castration resistant prostate cancer; fatty acid synthase