Inhibition of P-glycoprotein activity and reversal of multidrug resistance in vitro by rosemary extract

C. A. Plouzek, H. P. Ciolino, R. Clarke, G. G. Yeh

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

The transmembrane transport pump P-glycoprotein (Pgp) causes the efflux of chemotherapeutic agents from cells and is believed to be an important mechanism in multidrug resistance (MDR) in mammary tumours. In the present study we demonstrate that an extract of the common dietary herb rosemary (Rosemarinus officinalis Labiatae), increases the intracellular accumulation of commonly used chemotherapeutic agents, including doxorubicin (DOX) and vinblastine (VIN), in drug-resistant MCF-7 human breast cancer cells which express Pgp. Rosemary extract (RE) inhibits the efflux of DOX and VIN, which are known to be substrates of Pgp, but does not affect accumulation or efflux of DOX in wild type MCF-7 cells, which lack Pgp. Treatment of drug-resistant cells with RE increases their sensitivity to DOX, which is consistent with an increased intracellular accumulation of the drug. RE blocks the binding of the VIN analogue azidopine to Pgp. Thus, it appears that RE directly inhibits Pgp activity by inhibiting the binding of drugs to Pgp. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1541-1545
Number of pages5
JournalEuropean Journal of Cancer
Volume35
Issue number10
DOIs
StatePublished - Oct 1999
Externally publishedYes

Keywords

  • Breast cancer
  • Doxorubicin
  • Multidrug resistance
  • P-glycoprotein
  • Rosemary

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