Effects of Black Raspberries and Their Constituents on Rat Prostate Carcinogenesis and Human Prostate Cancer Cell Growth In Vitro

Abstract

Prostate cancer patients often use dietary supplements, such as black raspberries, which are a rich source of compounds with antioxidant and anticancer activity, particularly on gastrointestinal cancers. Feeding black raspberries inhibited mammary cancer induction in rats and growth of cancer cells in nude mice, indicating systemic bioavailability of bioactive compounds. We tested whether feeding black raspberries and its constituents would inhibit prostate cancer development. However, we did not find preventive effects in two rat prostate carcinogenesis models, even though the berry anthocyanin metabolite protocatechuic acid was detectable in their prostates. Black raspberry extract, the anthocyanin cyanidin-3-rutinoside and protocatechuic acid did not inhibit prostate cancer cell growth in vitro, but ellagic acid and its urolithin A metabolite did at high concentrations. Prostate cancer cell migration was not affected by these agents nor was growth in soft agar, except that ellagic acid reduced colony formation at physiological concentrations and protocatechuic acid at high concentrations. Low bioavailability of bioactive berry compounds and metabolites may limit exposure of tissues such as the prostate, since we found that cyanidin-3-rutinoside was not bioavailable to prostate cancer cells, but its aglycone cyanidin was and inhibited their growth. Thus, black raspberries are unlikely to prevent prostate cancer.

Authors’ Contributions

Conception and design: J.N. Eskra, M.C. Bosland

Development of methodology: J.N. Eskra, M.C. Bosland, M.J. Schlicht

Acquisition of data: J.N. Eskra, A. Dodge, M.J. Schlicht

Analysis and interpretation of data: J.N. Eskra, M.C. Bosland

Writing, review, and/or revision of the manuscript: J.N. Eskra, M.C. Bosland, M.J. Schlicht

Administrative, technical, or material support: M.J. Schlicht, A. Dodge

Study supervision: M.C. Bosland

Acknowledgments

Research support – Animal care services were provided by the Biological Resources Laboratory and histology services by the Research Resources Center – Research Histology and Tissue Imaging Core at the University of Illinois at Chicago both established with the support of the Vice Chancellor of Research.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Funding

This work was supported in part by the National Institutes of Health under Grant No. R21 CA152879-01A1 to MCB, and by a Pre-Doctoral Education for Clinical and Translational Scientists Fellowship from the UIC Center for Clinical and Translational Science under NIH Grant No. UL1TR002003 and a UIC Chancellor’s Research Fellowship to JNE.