Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or endothelial cells, and serve as a physical barrier to maintenance of homeostasis in body by controlling paracellular transport.
Claudins are the most important molecules of the TJs, but paradoxically these
proteins are frequently over-expressed in
cancers and their overexpression is implicated in the invasive potential of
cancer. Hence, we investigated the effects of
flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) on TJs and the expression of
claudins as well as
cancer invasion along with in LnCaP human
prostate cancer. FEOJ suppressed
cancer cell motility and invasiveness at the concentrations where FEOJ did not show anti-proliferative activity. FEOJ increased transepithelial electrical resistance (TER) associated with tightening TJs, and suppressed expression of
claudin proteins. Furthermore, FEOJ suppressed the activities of MMP-2 and -9 in a dose-dependent manner, which came from the activation of
tissue inhibitor of metalloproteinases (TIMPs) by FEOJ. FEOJ suppressed migration and invasion by suppressing PI3K/Akt signaling pathway. Taken together, this study suggest that FEOJ suppresses
cancer migration and invasion by tightening TJs through the suppression of
claudin expression, and by suppressing
MMPs in LnCaP human
prostate cancer cells, which at least in part results from the suppression of PI3K/Akt signaling pathway.