title: Naftopidil, a selective alpha-1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest.
abstract: Alpha-1 adrenoceptor antagonists are generally prescribed for benign prostate hyperplasia with lower urinary tract symptoms. Naftopidil, a selective alpha-1 adrenoceptor antagonist, is frequently used in Japan because it has fewer side effects. Here we demonstrate for the first time that naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines. The concentrations causing 50% inhibition (IC50) of cancer cell growth were 22.2 +/- 4.0 microM in androgen-sensitive LNCaP cells and 33.2 +/- 1.1 microM in androgen-insensitive PC-3 cells. FACS analysis revealed that cell growth inhibition by naftopidil was due to the arrest of the G1 cell cycle. Expressions of p27(kip1) and p21(cip1) were significantly increased in LNCaP cells treated with naftopidil. In PC-3 cells, naftopidil induced p21(cip1) but not p27(kip1). In vivo, oral administration of naftopidil to nude mice inhibited the growth of PC-3 tumors as compared to vehicle-treated controls. These results suggest that naftopidil may be useful in the chemoprevention of prostate cancer and the intervention of hormone refractory prostate cancer.
authors.affiliation: Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kanda
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Ishii
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Imamura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kanai
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Arima
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugimura
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009281:Naphthalenes / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D010879:Piperazines / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D009281:Naphthalenes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C064357:naftopidil