Inhibition of anticancer drug efflux transporter P-glycoprotein by rosemary phytochemicals

Pharmacol Res. 2010 Mar;61(3):259-63. doi: 10.1016/j.phrs.2009.11.010. Epub 2009 Nov 26.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Daunorubicin / metabolism
  • Humans
  • KB Cells
  • Multidrug Resistance-Associated Proteins
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Plant Leaves / physiology
  • Rosmarinus / chemistry*
  • Rosmarinus / physiology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Multidrug Resistance-Associated Proteins
  • Plant Extracts
  • multidrug resistance-associated protein 1
  • Daunorubicin