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

Gabriella Spengler, Daniella Takács, Ádám Horváth, Zsuzsanna Riedl, György Hajós, Leonard Amaral, József Molnár

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1737-1742
Number of pages6
JournalAnticancer research
Volume34
Issue number4
Publication statusPublished - Apr 1 2014

Keywords

  • ABCB1
  • ATP-binding cassette protein B1
  • Ethidium bromide
  • Mouse T-lymphoma cell lines
  • Multidrug resistance
  • P-glycoprotein
  • Phenothiazines
  • Rhodamine 123
  • Thioridazine
  • Verapamil

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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