Effects of Black Raspberries and Their Ellagic Acid and Anthocyanin Constituents on Taxane Chemotherapy of Castration-Resistant Prostate Cancer Cells

• Published in: Scientific reports 2019-03, Vol.9 (1), p.4367, Article 4367
• Main Authors: Eskra, Jillian N., Schlicht, Michael J., Bosland, Maarten C.
• Format: Article
• Language: English
• Subjects: 13/106; 13/51; 14/34; 64/60; 692/4025/1752; 692/4028/67/589/466; 82/103; 82/29; Acids; Animals; Anthocyanins - administration & dosage; Anthocyanins - pharmacology; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Cancer therapies; Castration; Cell culture; Chemotherapy; Cytotoxicity; Dietary supplements; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm - drug effects; Ellagic acid; Ellagic Acid - administration & dosage; Ellagic Acid - pharmacology; Growth inhibition; Humanities and Social Sciences; Humans; Male; Metabolites; Mice; Microtubules - metabolism; multidisciplinary; P-Glycoprotein; Plant Extracts - chemistry; Plant Extracts - pharmacology; Polymerization; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - metabolism; Protein Binding; Protein Multimerization; Protocatechuic acid; Rubus - chemistry; Science; Science (multidisciplinary); Taxanes; Taxoids - administration & dosage; Taxoids - pharmacology; Tubulin; Tubulin - metabolism; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-39589-1

Cancer patients often use dietary supplements while on therapy, but little is known about interactions of supplements with cancer chemotherapy. Black raspberries (BRB) have anti-cancer effects, but have not been evaluated for interference with chemotherapy for castrate-resistant prostate cancer (CRPC). Here we studied whether BRB and some of their constituents interact with docetaxel and cabazitaxel on CRPC cells in culture and implanted into nude mice. Ellagic acid increased, but BRB extract inhibited, microtubule assembly. Ellagic acid decreased tubulin polymerization by cabazitaxel and bound to tubulin. Ellagic acid, its metabolite urolithin A, BRB extract, and the anthocyanin metabolite protocatechuic acid (PCA) did not alter cytotoxicity of taxanes. Ellagic acid inhibited drug efflux in CRPC cells, but BRB extract and PCA did not. None of these compounds altered CYP3A4 activity. Although dietary ellagic acid did not alter the tumor growth inhibition by docetaxel of xenografted 22Rv1 cells, ellagic acid has the potential to interfere with taxane chemotherapy by reducing tubulin polymerization while inhibiting P-glycoprotein drug efflux. These data are cause for concern of consuming ellagic acid during treatment for CRPC and indicate need for further research, but BRB consumption appears safe.