Anti-invasive activity of diallyl disulfide through tightening of tight junctions and inhibition of matrix metalloproteinase activities in LNCaP prostate cancer cells

Abstract

Diallyl disulfide (DADS) is a major component of an oil-soluble allyl sulfide garlic (Allium sativum) deriv- ative, which has been shown to exert a potential for anti-cancer activity. However, the biochemicalmech- anisms underlying DADS-induced anti-invasiveness and anti-metastasis have not been thoroughly studied. In this study, we investigated the effect of DADS on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human prostate carcinoma LNCaP cells. Inhibitory effects of DADS on cell motility and invasiveness were found to be associated with increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance (TER). Additionally, immu- noblotting results indicated that DADS repressed the levels of the claudin proteins, which are major com- ponents of TJs that play a key role in control and selectivity of paracellular transport. Furthermore, the activities of matrix metalloproteinase (MMP)-2 and -9 in LNCaP cells were dose-dependently inhibited by treatment with DADS, and this was also correlated with a decrease in expression of their mRNA and proteins. Although further studies are needed, the present study indicates that TJs and MMPs are crit- ical targets of DADS-induced anti-invasiveness in human prostate cancer LNCaP cells. 2010 Elsevier Ltd. All rights reserved. Keywords: DADS Invasion Tight junctions Matrix metalloproteinases