Multidrug Resistance Reversing Activity of Newly Developed Phenothiazines on P-glycoprotein (ABCB1)-related Resistance of Mouse T-Lymphoma Cells

Spengler, Gabriella and Takács, Daniella and Horváth, Ádám and Riedl, Zsuzsanna and Hajós, György and Amaral, Leonard and Molnár, József (2014) Multidrug Resistance Reversing Activity of Newly Developed Phenothiazines on P-glycoprotein (ABCB1)-related Resistance of Mouse T-Lymphoma Cells. Anticancer Research, 34. pp. 1737-1742. ISSN 0250-7005 (print), 1791-7530 (online)

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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 Pglycoprotein) 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.

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