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

G. Spengler, Jadwiga Handzlik, I. Ocsovszki, Miguel Viveiros, Katarzyna Kieć-Kononowicz, J. Molnár, Leonard Amaral

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3285-3288
Number of pages4
JournalAnticancer Research
Volume31
Issue number10
Publication statusPublished - Oct 2011

Fingerprint

Hydantoins
Colon
Adenocarcinoma
Apoptosis
Carcinoma
T-Cell Lymphoma
P-Glycoprotein
Verapamil
Doxorubicin
Drug Therapy
Pharmaceutical Preparations
Neoplasms

Keywords

  • ABCB1 transporter
  • Apoptosis
  • Colo 205 and Colo 320 colon adenocarcinoma cells
  • Efflux pump
  • Hydantoin derivatives
  • Multidrug resistance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis. / Spengler, G.; Handzlik, Jadwiga; Ocsovszki, I.; Viveiros, Miguel; Kieć-Kononowicz, Katarzyna; Molnár, J.; Amaral, Leonard.

In: Anticancer Research, Vol. 31, No. 10, 10.2011, p. 3285-3288.

Research output: Contribution to journalArticle

Spengler, G. ; Handzlik, Jadwiga ; Ocsovszki, I. ; Viveiros, Miguel ; Kieć-Kononowicz, Katarzyna ; Molnár, J. ; Amaral, Leonard. / Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis. In: Anticancer Research. 2011 ; Vol. 31, No. 10. pp. 3285-3288.
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