Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells

Oncol Res. 1992;4(8-9):359-65.


We have previously shown that efflux of cytotoxic drugs from multidrug resistant (MDR) cell lines can be quantitated at the single cell level using a sensitive fluorescence microscopy technique. Based on the structure of compounds which inhibited the efflux of Rhodamine-123 (Rho-123) using this methodology, we hypothesized that the antiemetic, antihistaminic agent benzquinamide (BZQ) would interfere with P-glycoprotein (P-gp) mediated drug transport and potentiate the effects of anticancer agents in MDR cell lines. We show that BZQ interferes with P-gp mediated drug efflux and increases drug accumulation in MDR cells using Rho-123 as a fluorescent probe. BZQ increases the cytotoxicity of chemotherapeutic agents to both human and hamster MDR cell lines in vitro. A slight increase in cytotoxicity to chemotherapeutic agents is also observed in the parental cell lines with BZQ. BZQ increases [3H]daunorubicin accumulation and inhibits the binding of [125I]iodoaryl azidoprazosin to the P-gp in MDR cells. BZQ is a new agent to increase the cytotoxic effects of anticancer agents in MDR cells and may ultimately prove useful as an adjunct in cancer chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Affinity Labels
  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Cricetinae
  • Drug Resistance
  • Drug Synergism
  • Humans
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Neoplasm Proteins / antagonists & inhibitors*
  • Phenotype
  • Protein Binding / drug effects
  • Quinolizines / pharmacology*
  • Rhodamine 123
  • Rhodamines / pharmacokinetics
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Affinity Labels
  • Antineoplastic Agents
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Quinolizines
  • Rhodamines
  • benzquinamide
  • Rhodamine 123