ORIGINAL ARTICLESNFκB-dependent regulation of urokinase plasminogen activator by proanthocyanidin-rich grape seed extract: effect on invasion by prostate cancer cellsUchino, Ryoji; Madhyastha, Radha; Madhyastha, Harishkumar; Dhungana, Sandra; Nakajima, Yuichi; Omura, Sayuri; Maruyama, MasugiAuthor Information Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan Received 2 November, 2009 Accepted 3 April, 2010 Correspondence to Dr Masugi Maruyama Tel: +81 985 85 1785; fax: +81 985 85 7932; e-mail: firstname.lastname@example.org Blood Coagulation & Fibrinolysis: September 2010 - Volume 21 - Issue 6 - p 528-533 doi: 10.1097/MBC.0b013e32833a9b61 Buy Metrics Abstract Tumor invasion and metastasis present major obstacles to successful control of androgen-independent prostate cancer. Cell migration is a fundamental aspect of cancer cell metastasis. Urokinase plasminogen activator (uPA) system is implicated in cell migration and cancer metastasis and has potential to be developed as therapeutic target. In recent years, efficacy of dietary nutrients in preventing and curing cancer has gained increasing attention. One such promising candidate is proanthocyanidin-rich grape seed extract (GSE). We investigated the efficacy of GSE in regulating uPA expression and cell migration using highly metastatic androgen-independent PC3 prostate cancer cells as a model. GSE down-regulated uPA as a function of concentration. Additional studies showed that GSE inhibited DNA-binding activity of the transcription factor nuclear factor kappa B (NFκB), which in turn decreased NFκB-dependent uPA transcription. Invasion assays revealed the inhibitory effect of GSE on PC3 cell migration. These in-vitro experiments demonstrate the therapeutic property of GSE as an antimetastatic agent by targeting uPA. © 2010 Lippincott Williams & Wilkins, Inc.