Apocynin, an NADPH oxidase inhibitor, suppresses rat prostate carcinogenesis

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...

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Bibliographic Details
Published in:Cancer science 2013-12, Vol.104 (12), p.1711-1717
Main Authors: Suzuki, Shugo, Shiraga, Kazuhide, Sato, Shinya, Punfa, Wanisa, Naiki‐Ito, Aya, Yamashita, Yoriko, Shirai, Tomoyuki, Takahashi, Satoru
Format: Article
Language:English
Subjects:
Acetophenones - pharmacology
Adenocarcinoma
Animals
Carcinogenesis - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Clusterin - biosynthesis
Cyclin D1 - biosynthesis
Down-Regulation
Enzyme Inhibitors - pharmacology
Extracellular Signal-Regulated MAP Kinases - metabolism
G1 Phase Cell Cycle Checkpoints - drug effects
Humans
Ki-67 Antigen - metabolism
Male
MAP Kinase Kinase Kinases - metabolism
MAP Kinase Signaling System
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - metabolism
Original
Oxidative Stress - drug effects
Prostate - drug effects
Prostate - pathology
Prostatic Neoplasms - enzymology
Prostatic Neoplasms - pathology
Rats
Rats, Sprague-Dawley
Rats, Transgenic
Reactive Oxygen Species - analysis
Reactive Oxygen Species - metabolism
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Summary: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. Apocynin, a NADPH oxidase inhibitor, suppressed prostate carcinogenesis in TRAP model with reduction of reactive oxygen species (ROS) generation and cell proliferation in vivo. it also inhibited ROS production and blocked cell growth by inducing G0/G1 arrest with down‐regulation of clusterin and cyclin D1 in LNCaP cells. These data suggest that apocynin possesses a chemopreventive potential for prostate cancer.
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.12292