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Anticancer Res. 2014 Apr;34(4):1737-41.

Multidrug resistance reversing activity of newly developed phenothiazines on P-glycoprotein (ABCB1)-related resistance of mouse T-lymphoma cells.

Author information

  • 1Institute of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary. spengler.gabriella@med.u-szeged.hu.

Abstract

BACKGROUND:

Phenothiazines have anticancer properties and are able to reverse the multidrug resistance of neoplastic cells by inhibiting the ATP-binding cassette, sub-family B (MDR/TAP), member 1 protein (ABCB1 or P-glycoprotein) activity.

MATERIALS AND METHODS:

A series of new phenothiazine derivatives was investigated regarding their ABCB1-modulating effect on multidrug resistant mouse T-lymphoma cells by rhodamine 123 accumulation assay and real-time ethidium bromide accumulation assay.

RESULTS:

The phenothiazine derivatives exhibited a potent anticancer effect on the parental cell line and on its multidrug-resistant mouse T-lymphoma subline overexpressing the ABCB1 transporter. The inhibition of the ABCB1 transporter in the presence of the newly-developed phenothiazines was greater than that for the known ABCB1 inhibitors thioridazine and verapamil.

CONCLUSION:

Based on the chemical structures and biological activity, compounds with bivalent sulfur atom in the phenothiazine ring demonstrated marked ABCB1-modulating effect, however, other derivatives with halogen or amide substitutions were ineffective.

KEYWORDS:

ABCB1; ATP-binding cassette protein B1; P-glycoprotein; Phenothiazines; ethidium bromide; mouse T-lymphoma cell lines; multidrug resistance; rhodamine 123; thioridazine; verapamil

PMID:
24692704
[PubMed - indexed for MEDLINE]
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