Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis

Anticancer Res. 2011 Oct;31(10):3285-8.

Abstract

Background: Hydantoin derivatives are very promising candidates to improve the efficacy of anticancer chemotherapy. Previously, we demonstrated that eight hydantoin derivatives inhibited the P-glycoprotein (ABCB1) efflux pump of mouse T-lymphoma cells, as well as acting synergistically with the anticancer drug doxorubicin.

Materials and methods: The activity of the hydantoin derivatives were investigated in another MDR cancer model, namely Colo 205/S sensitive and Colo 320/R resistant colon carcinoma cells respectively, having normal or overexpressed ABCB1 systems.

Results: Among the hydantoin derivatives evaluated, BS-1, MN-3 and JH-63 were the most effective ABCB1 transporter inhibitors at the concentration of 4 mg/l on the Colo 320/R cells, compared to the positive control, verapamil.

Conclusion: The derivatives did not induce apoptosis of Colo 320/R resistant colon carcinoma cells, indicating that these hydantoin compounds are potent efflux pump inhibitors (EPI) without affecting the signalling pathways that regulate apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adenocarcinoma / pathology*
  • Animals
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • Humans
  • Hydantoins / metabolism*
  • Hydantoins / pharmacology*
  • Mice
  • Rhodamine 123 / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Hydantoins
  • Rhodamine 123