Inhibition of P-glycoprotein transport function by N-acylphenothiazines

Olga Wesolowska, Joseph Molnár, Noboru Motohashi, Krystyna Michalak

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Multidrug resistance (mdr) constitutes the major obstacle to successful cancer treatment. The ability of fifteen newly-synthesised N-acylphenothiazine derivatives to inhibit the transport activity of P-glycoprotein was studied by flow cytometry in a resistant mouse lymphoma cell line. A standard functional assay with rhodamine 123 as a fluorescent substrate analogue was used. All derivatives proved to be effective inhibitors of rhodamine 123 outward transport, however their toxicity to the cells was not negligible. Phenothiazine maleates probably interact with transporter proteins of cancer cells by a different mechanism than other phenothiazine derivatives studied. The mdr reversal mechanism of phenothiazine acetylamides, methoxycarbonylamides and methylsulfonylamides is likely to involve modulator-cell membrane interactions since a connection between the compounds' hydrophobicity and their P-glycoprotein inhibition potency was observed. As a result of the present study a new group of mdr reversal agents was identified.

Original languageEnglish
Pages (from-to)2863-2868
Number of pages6
JournalAnticancer research
Volume22
Issue number5
Publication statusPublished - Sep 1 2002

Keywords

  • Flow cytometry
  • Multidrug resistance
  • P-glycoprotein
  • Phenothiazine derivatives

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wesolowska, O., Molnár, J., Motohashi, N., & Michalak, K. (2002). Inhibition of P-glycoprotein transport function by N-acylphenothiazines. Anticancer research, 22(5), 2863-2868.