Quercetin as a potential modulator of P-glycoprotein expression and function in cells of human pancreatic carcinoma line resistant to daunorubicin

Molecules. 2010 Feb 9;15(2):857-70. doi: 10.3390/molecules15020857.

Abstract

P-glycoprotein (P-gp) is one of the ABC transporters responsible for the resistance of several tumours to successful chemotherapy. Numerous agents are capable of interfering with the P-gp-mediated export of drugs but unfortunately most of them produce serious side effects. Some plant polyphenols, including the flavonol quercetin (Q), manifest anti-neoplastic activity mainly due to their influence on cell cycle control and apoptosis. Reports are also available which show that Q may intensify action of cytostatic drugs and suppress the multidrug resistance (MDR) phenomenon. The study aimed at determination if Q sensitizes cells resistant to daunorubicin (DB) through its effect on P-gp expression and action. The experiments were conducted on two cell lines of human pancreatic carcinoma, resistant to DB EPP85-181RDB and sensitive EPP85-181P as a comparison. Cells of both lines were exposed to selected concentrations of Q and DB, and then membranous expression of P-gp and its transport function were examined. The influence on expression of gene for P-gp (ABCB1) was also investigated. Results of the studies confirmed that Q affects expression and function of P-gp in a concentration-dependent manner. Moreover it decreased expression of ABCB1. Thus, Q may be considered as a potential modulator of P-gp.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Blotting, Western
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Daunorubicin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Fluoresceins / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Quercetin / chemistry
  • Quercetin / pharmacology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Fluoresceins
  • Quercetin
  • fluorexon
  • Daunorubicin