Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashi-jima, Akiha-ku, Niigata 956-8603, Japan.
Pharmacol Res. 2010 Mar;61(3):259-63. doi: 10.1016/j.phrs.2009.11.010. Epub 2009 Nov 26.
The effects of dietary antioxidative and chemopreventive rosemary phytochemicals on the function of the human drug efflux transporter P-glycoprotein (MDR1, ABCB1) and multidrug resistance protein 1 (MRP1, ABCC1) were investigated using P-glycoprotein-overexpressing human carcinoma KB-C2 cells and human MRP1 gene-transfected KB/MRP cells. The effects of natural phytochemicals found in rosemary such as carnosic acid, carnosol, rosmarinic acid, and ursolic acid were investigated. The accumulation of daunorubicin or rhodamine 123, fluorescent substrates of P-glycoprotein, in KB-C2 cells increased in the presence of carnosic acid, carnosol, and ursolic acid in a concentration-dependent manner. In contrast, carnosic acid, carnosol, rosmarinic acid, and ursolic acid had no effects on the accumulation of calcein, a fluorescent substrate of MRP1, in KB/MRP cells. The ATPase activities of P-glycoprotein were stimulated by carnosic acid, carnosol, and ursolic acid. KB-C2 cells were sensitized to vinblastine cytotoxicity by carnosic acid, showing that carnosic acid reverses multidrug resistance. These results suggest that rosemary phytochemicals, such as carnosic acid, have inhibitory effects on anticancer drug efflux transporter P-glycoprotein and may become useful to enhance the efficacy of cancer chemotherapy.
研究了膳食抗氧化和化学预防的迷迭香植物化学物质对人药物外排转运蛋白 P-糖蛋白（MDR1，ABCB1）和多药耐药蛋白 1（MRP1，ABCC1）功能的影响，使用 P-糖蛋白过表达的人癌 KB-C2 细胞和人 MRP1 基因转染的 KB/MRP 细胞进行了研究。研究了迷迭香中发现的天然植物化学物质，如鼠尾草酸、鼠尾草酚、迷迭香酸和熊果酸的作用。在存在鼠尾草酸、鼠尾草酚和熊果酸的情况下，KB-C2 细胞中柔红霉素或罗丹明 123（P-糖蛋白的荧光底物）的积累呈浓度依赖性增加。相比之下，鼠尾草酸、鼠尾草酚、迷迭香酸和熊果酸对 KB/MRP 细胞中 calcein（MRP1 的荧光底物）的积累没有影响。鼠尾草酸、鼠尾草酚和熊果酸刺激 P-糖蛋白的 ATP 酶活性。鼠尾草酸使 KB-C2 细胞对长春碱细胞毒性敏感，表明鼠尾草酸逆转了多药耐药性。这些结果表明，迷迭香植物化学物质，如鼠尾草酸，对抗癌药物外排转运蛋白 P-糖蛋白具有抑制作用，可能成为增强癌症化疗疗效的有用物质。
