title: Cytochrome P450 17A1 inhibitor abiraterone attenuates cellular growth of prostate cancer cells independently from androgen receptor signaling by modulation of oncogenic and apoptotic pathways.
abstract: Abiraterone provides significant survival advantages in prostate cancer (PC), however, the current understanding of the molecular mechanisms of abiraterone is still limited. Therefore, the abiraterone impact on androgen receptor (AR)-positive LNCaP and AR-negative PC-3 cells was assessed by cellular and molecular analyses. The present study demonstrated, that abiraterone treatment significantly decreased cell growth, AR expression, and AR activity of AR-positive LNCaP cells. Notably, AR-negative PC-3 cells exhibited comparable reductions in cellular proliferation, associated with DNA fragmentation and pro-apoptotic modulation of p21, caspase-3, survivin, and transforming growth factor β (TGFβ). Our observations suggest that the attenuation of AR signaling is not the only rationale to explain the abiraterone anticancer activity. Abiraterone efficacy may play a more global role in PC progression control than originally hypothesized. In this regard, abiraterone is not only a promising drug for treatment of AR-negative PC stages, even more, abiraterone may represent an alternative for treatment of other malignancies besides prostate cancer.
authors.affiliation: Department of Urology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Grossebrummel
authors.affiliation: Department of Urology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Peter
authors.affiliation: Department of Urology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Mandelkow
authors.affiliation: Department of Urology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Department of Obstetrics and Gynaecology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Damian
authors.initials: D
authors.lastname: Muzzio
authors.affiliation: Department of Urology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Zimmermann
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Walther
authors.affiliation: Department of Obstetrics and Gynaecology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Jensen
authors.affiliation: Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, D-32545 Bad Oeynhausen, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Knabbe
authors.affiliation: Department of Obstetrics and Gynaecology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Urology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Burchardt
authors.affiliation: Department of Urology, University Medicine Greifswald, D-17475 Greifswald, Germany.
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Stope
mesh_terms: D000736:Androstenes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000077022:Survivin; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000736:Androstenes; C107489:BIRC5 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D011944:Receptors, Androgen; D000077022:Survivin; D016212:Transforming Growth Factor beta; D003577:Cytochrome P-450 Enzyme System; D053148:Caspase 3; C089740:abiraterone