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Updated: Apr 11, 2026

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Reversal of ABCB1-related Multidrug Resistance of Colonic Adenocarcinoma Cells by Phenothiazines

Daniella Takács1, Ákos Csonka2, Ádám Horváth2

  • 1Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

Anticancer Research
|May 31, 2015
PubMed
Abstract

Insights

Phenothiazine derivatives show potent anticancer effects and reverse multidrug resistance (MDR) in colon cancer cells. These compounds inhibit ATP-binding cassette (ABC) transporters more effectively than verapamil, suggesting potential as MDR-reversing agents.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Overexpression of ATP-binding cassette (ABC) drug transporters is a primary cause of reduced anticancer agent efficacy.
  • Phenothiazines and related compounds can sensitize multidrug-resistant (MDR) cells to chemotherapy.

Purpose of the Study:

  • To investigate the anticancer and MDR-reversing effects of phenothiazine derivatives on colonic adenocarcinoma cells.
  • To evaluate the potential of these derivatives as modulators of ABCB1 transporter activity.

Main Methods:

  • Assessed anti-proliferative and cytotoxic effects using the thiazolyl blue tetrazolium bromide (MTT) assay.
  • Measured ATP-binding cassette subfamily B member 1 (ABCB1) activity via rhodamine 123 accumulation using flow cytometry.

Main Results:

  • Phenothiazine derivatives demonstrated significant cytotoxic effects on both sensitive and MDR colon adenocarcinoma cell lines.
  • Inhibition of ABCB1 transporter activity by phenothiazine derivatives surpassed that of verapamil, a known ABCB1 inhibitor.

Conclusions:

  • Phenothiazine derivatives exhibit synergistic effects when combined with doxorubicin.
  • These derivatives hold promise as effective inhibitors of the ABCB1 transporter, potentially overcoming multidrug resistance in cancer therapy.
Keywords:
MDRP-glycoprotein (ABCB1)Phenothiazinesapoptosiscolon adenocarcinomadoxorubicinmultidrug resistancerhodamine 123verapamil

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