Oligomeric Proanthocyanidin Complexes (OPC) Exert Anti-Proliferative and Pro-Apoptotic Effects on Prostate Cancer Cells

BACKGROUND. Oligomeric proanthocyanidin complexes (OPC) are extracted from grape seeds or maritime pine bark and have been used for enhancement of capillary stability and lymphatic drainage. Since a role for OPC in cancer prevention was postulated, we asked whether they have an effect on prostate cancer cells. METHODS. Cell proliferation was determined by 3 H-thymidine assay and cell cycle status was analyzed on a flow cytometer. Expression of regulators of proliferation and apoptosis was determined by Western blot. RESULTS. We found that androgen-responsive cells LNCaP are more sensitive to OPC in terms of inhibition of proliferation in comparison to androgen receptor-negative PC3 or DU145 cells. Treatment with OPC resulted in a decrease in the percentage of LNCaP cells in the S phase and an increase in the percentage of cells in sub G1 phase. The anti-proliferative and proapoptotic effect of OPC in the LNCaP cell line was associated with down-regulation of expression of the androgen receptor. Interestingly, similar regulatory effects of OPC, such as inhibition of expression of cyclin-dependent kinases and cyclins and stimulation of tumor suppressors p21 and p27, were seen in LNCaP and PC3 cells. Favorable changes in the Bcl-2/Bax ratio were observed in LNCaP and PC3 cells after the treatment with OPC. OPC caused an increase of phosphorylated mitogen-activated protein kinase p44 and p42, thus suggesting induction of cellular differentiation. CONCLUSIONS. We conclude that OPC is a candidate that fulfills criteria for chemopreventive strategies in prostate cancer that might be established in following in vivo studies. Prostate 68: 1647-1654, 2008. (C) 2008 Wiley- Liss, Inc.