The beta-carboline alkaloid harmine inhibits BCRP and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells

Phytother Res. 2010 Jan;24(1):146-9. doi: 10.1002/ptr.2860.

Abstract

Multidrug resistance (MDR), mediated by highly expressed ABC transporters, is one of the most important mechanisms in tumor cells. Breast cancer resistance protein (BCRP) is a member of the ABC transporter family. This transporter expels different kinds of lipophilic anticancer drugs, which have diffused into the cells. In this study, 96-well plate based assays and flow cytometry analysis were employed to screen natural products for BCRP inhibition. The beta-carboline alkaloid harmine inhibited BCRP in a BCRP overexpressing breast cancer cell line (MDA-MB-231). Harmine reduced resistance to the anticancer drugs mitoxantrone and camptothecin mediated by BCRP and might be an interesting new reversal agent. Harmine did not inhibit P-glycoprotein (P-gp) mediated drug efflux.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism*
  • Camptothecin / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Harmine / pharmacology*
  • Humans
  • Mitoxantrone / pharmacology*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Neoplasm Proteins / metabolism*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Harmine
  • Mitoxantrone
  • Camptothecin