Abstract 2131: Effects of black raspberries and their constituents on rat prostate carcinogenesis and human prostate cancer cell growth

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Black raspberries (BRBs) and their constituents may inhibit human GI tract cancers and prevent breast cancer in a rat model. Anthocyanins and polyphenols in BRBs are responsible for their anti-cancer effects. Berries and other fruits are used as dietary supplements by cancer patients. As prostate cancer remains a major health problem, it is thus important to determine whether BRBs or BRB constituents may prevent or treat this malignancy. We previously reported (AACR Ann Mtg 2013) that the BRB anthocyanin metabolite protocatechuic acid (PCA) was detectable in the prostate of rats fed BRB, indicating that it reaches this tissue, but BRB consumption by Wistar rats did not prevent prostate cancer induced by MNU and chronic testosterone treatment. We now studied the effect of feeding AIN-93M diet containing 5% or 10% lyophilized BRB powder (exchanged for starch) on induction of prostate cancer in NBL rats by chronic testosterone & 17β-estradiol treatment via SC Silastic implants. Incidence of adenocarcinomas arising from periurethral prostatic ducts was similar in rats fed control diet and those fed berry-containing diets (73-90%), as was tumor multiplicity (1.7-1.8 tumors per prostate). In contrast, we previously found that cyanidin-3-rutinoside, the most abundant anthocyanin in BRBs, inhibits growth of LAPC-4 human prostate cancer cells. We now used PC-3 and LNCaP prostate cancer cells to study effects of ethanolic extract of lyophilized BRB powder and major BRB constituents: the polyphenol ellagic acid (EA), cyanidin-3-rutinoside, and PCA. Growth rates were measured by hemocytometer counting with trypan blue exclusion. BRB extract (1 µg/ml to 1 mg/ml) inhibited viability of LNCaP cells dose-dependently, but linear trend was not significant (p=0.09). Similar, but also not quite significant, decreases in LNCaP cell numbers were caused by PCA and EA, while EA increased the number of dead cells (ANOVA p=0.0471, linear trend p=0.0385). No significant changes occurred in PC-3 cell viability with any of the treatments. Effects on anchorage independent growth of PC-3 cells were assessed by soft agar colony forming assays. A dose-dependent reduction in the number of colonies occurred after EA treatment (ANOVA p=0.0065, linear trend p=0.0007) and BRB extract (ANOVA p<0.0001, linear trend p<0.0001), but no change in colony formation of cells treated with cyanidin-3-rutinoside or PCA. Compared to vehicle, BRB at 1 mg/ml maximally reduced colonies by 50%, and 3.0 µg/ml EA reduced colonies by 39%. No effects on cell migration of PC-3 cells, assessed by wound healing assays, were found for any of the treatments. Thus, BRBs may be beneficial for treatment of prostate cancer and EA is at least partially responsible for the anti-cancer activity of BRBs, but, surprisingly, cyanidin-3-rutinoside and protocatechuic acid did not have significant effects. (Supported by NIH Grant R21 CA152879). Citation Format: Jillian N. Eskra, Michael J. Schlicht, Maarten C. Bosland. Effects of black raspberries and their constituents on rat prostate carcinogenesis and human prostate cancer cell growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2131. doi:10.1158/1538-7445.AM2014-2131