Cranberry proanthocyanidins affect human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators

Abstract

The effects of a proanthocyanidin‐enriched fraction (PACs) from American cranberry(V. macrocarpon) on DU145 cancer cells’ behavior in vitro was studied. PACs was characterized by MALDI‐TOF MS to contain PAC‐oligomers ranging in size from 2–12 epicatechin units with at least one A type linkage. PACs (25 ug/mL) decreased cellular viability by ~30 % post 6h.of treatment. PACs (post 6h. exposure) increased the proportion of cells in G2‐M and decreased the proportion of cells in G1. These alterations in cell cycle were associated with changes in cell cycle regulatory proteins and other cell cycle associated activities. PACs decreased the protein expression levels of cyclin A & cyclin B1 and increased the expression of cyclin D1 & cyclin E. PACs treatment resulted in an increase in the protein expression levels of CDK2 & CDK4. Decreased p21, p16, & pRBp107 protein expression levels and increased p27 protein expression levels were evident in response to PACs treatment with no apparent alteration in the levels of pRbp130 protein. These findings demonstrate that PACs contribute to the cranberry mediated alterations in cell cycle proteins. Cranberry extracts can affect the behavior of DU145 prostate cancer cells in vitro further supporting the potential health benefits associated with cranberries. [N.C.I.C.‐ CCS, P.E‐HRP, The Cranberry Institute (Wisconsin Cranberry Board), Telus MRFD Prostate Cancer Fund (PEI Division)]