Grape-Seed Procyanidins Inhibit the In Vitro Growth and Invasion of Pancreatic Carcinoma Cells

Objectives: Grape-seed procyanidins (GSPs) can inhibit cell proliferation and invasiveness in various human cancers. However, the effect of GSP on pancreatic carcinoma cells has not been investigated. Methods: Pancreatic carcinoma cell lines MIA PaCa-2 and BxPC-3 treated with GSP were assessed for viability by trypan blue exclusion, for cell cycle distribution by flow cytometry, for increased apoptosis by annexin V labeling, for their adhesion and invasion potential by evaluating their ability to penetrate through a matrix gel-coated Boyden chamber, and for changes in the levels of proteins involved in cellular events by immunoblotting. Results: Grape-seed procyanidin inhibited MIA PaCa-2 and BxPC-3 proliferation in a dose-dependent manner and induced G(1)-phase arrest of the cell cycle in BxPC-3 or mitochondria-mediated apoptosis in MIA PaCa-2. Grape-seed procyanidin also inhibited the adhesion and invasion potential of both cell lines in a dose-dependent manner, which are associated with the suppression of metalloproteases matrix metalloproteinase 9 or 2 (MMP-9 or -2) expression. Conclusions: Grape-seed procyanidin inhibited the proliferation of pancreatic carcinoma cells by cell cycle blockage or apoptotic induction. The invasiveness was also suppressed by GSP through down-regulation of MMP-2 or MMP-9 in pancreatic carcinoma cells. Grape-seed procyanidin is a potential chemotherapeutic or preventive agent for pancreatic carcinoma.