Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Department of Urology, Johns Hopkins University, Baltimore, MD, USA.
Sci Rep. 2019 Mar 13;9(1):4367. 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.
癌症患者在治疗过程中经常使用膳食补充剂，但对于补充剂与癌症化疗的相互作用知之甚少。黑覆盆子（BRB）具有抗癌作用，但尚未评估其对去势抵抗性前列腺癌（CRPC）化疗的干扰。在这里，我们研究了 BRB 及其一些成分是否会与多西他赛和卡巴他赛在体外培养的 CRPC 细胞和植入裸鼠中相互作用。鞣花酸可增加，但 BRB 提取物可抑制微管组装。鞣花酸可降低卡巴他赛诱导的微管蛋白聚合，并与微管蛋白结合。鞣花酸、其代谢物尿石素 A、BRB 提取物和原儿茶酸（PCA）代谢物均不改变紫杉烷的细胞毒性。鞣花酸可抑制 CRPC 细胞的药物外排，但 BRB 提取物和 PCA 则不能。这些化合物均不改变 CYP3A4 活性。尽管膳食鞣花酸并未改变异种移植的 22Rv1 细胞中多西他赛的肿瘤生长抑制作用，但鞣花酸通过减少微管蛋白聚合并抑制 P-糖蛋白药物外排，具有干扰紫杉烷化疗的潜力。这些数据引起了人们对 CRPC 治疗期间消耗鞣花酸的关注，并表明需要进一步研究，但 BRB 的消耗似乎是安全的。
