Proanthocyanidins from cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase expression in prostate cancer cells by affecting multiple cell signaling pathways

Abstract

This study examined the effects of a proanthocyanidin‐enriched fraction (PAC) from cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells in vitro. MMP‐2/−9 activity was inhibited by PAC in a dose/time dependent manner. PAC (25 ug/mL) decreased cellular viability 30% post 6 h.of treatment and had no significant effect on cellular viability post 3 h. Treatment of DU145 cells with PAC for 3 h. resulted in increased expression of p‐p38, pERK‐1, pERK‐2 protein levels. Increased JNK1 and decreased JNK2 protein expression occurred in response to PAC with corresponding alterations in p‐JNK1 and p‐JNK2. PAC treatment decreased protein expression levels of AKT, p‐AKT, P‐I‐3 kinase p85/p110 proteins. Treatment of DU145 cells with PAC resulted in inhibition of translocation of NF‐kB as suggested by decreased protein expression of p65 in the nuclear fraction. No apparent change in IkB alpha protein levels were noted. Decreased protein levels of p‐IkB alpha were observed. PAC fraction has the ability to inhibit MMP‐2/−9 activity at a concentration which is not cytotoxic to these cells suggesting that PACs inhibit MMP activity levels in DU145 cells in a targeted manner independent of cellular cytotoxicity effects. (N.C.I.C.‐ Canadian Cancer Society, P.E.I. Health Research Program, The Cranberry Institute (Wisconsin Board) funded)