title: Apocynin, an NADPH oxidase inhibitor, suppresses progression of prostate cancer via Rac1 dephosphorylation.
abstract: Recently, considerable evidence has been generated that oxidative stress contributes to the etiology and pathogenesis of prostate cancer. The present study focused on the effects of apocynin, an inhibitor of the NADPH oxidase which generates intracellular superoxide, on a rat androgen-independent prostate cancer cell line (PLS10) in vitro and in vivo. Apocynin significantly inhibited cell proliferation of PLS10 cells via G1 arrest of the cell cycle in vitro. Surprisingly, it did not affect reactive oxygen species (ROS) but inhibited phosphorylation of Rac1, one component of the NADPH oxidase complex. A Rac1 inhibitor, NSC23766, also inhibited cell proliferation, and both apocynin and NSC23766 reduced phosphorylation of Rac1 and NF-κB, as well as cyclin D1. Furthermore, in a xenograft model of prostate cancer with PLS10, apocynin suppressed tumor growth and metastasis in a dose dependent manner in vivo, with reduction of cell proliferation and vessel number in the tumors. Expression and secretion of vascular endothelial growth factor (VEGF) were reduced by apocynin treatment in vivo and in vitro, respectively. In conclusion, despite no apparent direct relationship with oxidative stress, apocynin inhibited growth of androgen-independent prostate cancer in vitro and in vivo. Apocynin thus warrants further attention as a potential anti-tumor drug.
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Graduate School of Medicine, Nagoya City University, Nagoya, Japan; Pathology Division, Nagoya City East Medical Center, Nagoya, Japan. Electronic address: shugo@med.nagoya-cu.ac.jp.
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Pornsiri
authors.initials: P
authors.lastname: Pitchakarn
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C056165:acetovanillone; D019255:NADPH Oxidases; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: Apocynin; Cancer progression; NADPH oxidase; Prostate cancer; Rac1