title: Apocynin, an NADPH oxidase inhibitor, suppresses rat prostate carcinogenesis.
abstract: Recent evidence suggests that oxidative stress contributes to the pathogenesis of prostate cancer. The present study focused on the effect of apocynin, an inhibitor of NADPH oxidase, on prostate carcinogenesis using the transgenic rat for adenocarcinoma of prostate (TRAP) model. There were no toxic effects with apocynin treatment. The percentages and numbers of carcinomas in both the ventral and lateral prostate were significantly reduced by apocynin treatment, with dose dependence. Reduction of reactive oxygen species by apocynin was confirmed by immunohistochemistry of 8-OHdG and dihydroethidium staining. Positivity of Ki67 was significantly reduced by apocynin treatment, and downregulation of clusterin expression, as well as inactivation of the MEK-ERK1/2 pathway, was a feature of the apocynin treated groups. In human prostate cancer cell line LNCaP, apocynin also inhibited reactive oxygen species production and blocked cell growth by inducing G0/G1 arrest with downregulation of clusterin and cyclin D1. These data suggest that apocynin possesses chemopreventive potential against prostate cancer.
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Pathology Division, Nagoya City East Medical Center, Nagoya, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Shiraga
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.forename: Wanisa
authors.initials: W
authors.lastname: Punfa
authors.forename: Aya
authors.initials: A
authors.lastname: Naiki-Ito
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000230:Adenocarcinoma; D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051152:Clusterin / Q000096:biosynthesis; D019938:Cyclin D1 / Q000096:biosynthesis; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism
chemical_list: D000098:Acetophenones; C530106:Ccnd1 protein, rat; D051152:Clusterin; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D017382:Reactive Oxygen Species; D019938:Cyclin D1; C056165:acetovanillone; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases