Diallyl sulfide, diallyl disulfide and diallyl trisulfide inhibit matrix metalloproteinase‐2, ‐7 and ‐9 expressions in human colon cancer cells through a cyclooxygenase‐2‐dependent mechanism

Abstract

Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are major components of garlic. They exhibit antiproliferative and anticancer activities but underlying molecular mechanisms are poorly understood. The purpose of this study was to determine whether DAS, DADS and DATS affected matrix metalloproteinases expression which is associated with the expression of cyclooxygenases-1 and -2 (COX-1 and COX-2) and the production of prostaglandin E2 (PGE2) in human colon cancer colo 205 cells in vitro. The enzyme cyclooxygenase-2 (COX-2) is abundantly expressed in colon cancer cells and plays a key role in colon tumorigenesis. In the presence of DAS, DADS and DATS in culture colo 205 cells for various incubation, it was found that DAS, DADS and DATS inhibited the expression of MMP-2, -7 and-9, respectively and three agents inhibited the expressions of COX-2 and PGE2 but they did not affect the expression of COX-1. Furthermore, DAS, DADS and DATS affected the expressions of MMPs and COX-2 via the inhibition of NF-£eB. NF-£eB underwent inhibition by DAS, DADS and DATS which was correlated with sequential suppression of the I£eB kinase activity, I£eB phosphorylation, p65 phosphorylation, p65 nuclear translocation and p65 acylation in colo 205 cells. As a whole, our results show that the decrease of MMP-2, -7 and -9 expressions by DAS, DADS and DATS requires prior down-regulation of COX-2 which went through the I£eB phosphorylation and remained subsequently inactive.