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

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.

• Authors: Gabriella Spengler, Jadwiga Handzlik, Imre Ocsovszki, Miguel Viveiros, Katarzyna Kiec-Kononowicz, Joseph Molnar, Leonard Amaral
• Journal: Anticancer research (Anticancer Res) Vol. 31 Issue 10 Pg. 3285-8 (Oct 2011) ISSN: 1791-7530 [Electronic] Greece
• PMID: 21965738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, pathology)
• Humans
• Hydantoins (metabolism, pharmacology)
• Mice
• Rhodamine 123 (metabolism)