Abstract
Cranberry can slow the growth of DU145 cells by inhibiting cell proliferation and also by apoptosis induction. Apoptosis may occur either via the mitochondrial‐mediated intrinsic pathway or death‐receptor mediated extrinsic pathway. This study investigated how a proanthocyanidin‐enriched fraction (PAC) from cranberry may regulate this complex process. PAC contained proanthocyanidin oligomers (major ones appear to be dimers, trimers & tetramers) (with 2–8 epicatechin units, with at least one A‐type linkage between units). PAC treatment resulted in a dose dependent inhibition of Bcl‐2, Bax, and Bid protein levels coupled with an induction of tBid protein. PAC also inhibits Smac/DIABLO levels. PAR‐4 protein levels increased in response to PAC. PAC resulted in a dose dependent induction of cytochrome ‐C in total cellular extract and cytochrome‐C protein expression also increased in mitochondrial extracts. Increased PARP protein expression occurred in response to PAC (25 ug/mL). PAC inhibited Fas‐L, FADD, and TRAIL protein expression levels whereas Fas protein levels were not affected by PAC. These results suggest that PAC is inducing apoptosis in DU145 cells via the intrinsic pathway and ensures this occurs by specifically inhibiting the extrinsic pathway of apoptosis.(N.C.I.C‐ Canadian Cancer Society, P.E.I. Heath Research Program, Cranberry Institute (Wisconsin Board) funded)
Published Version
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