Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression

Aniko Hevér, Christiane Santelli-Rouvier, Pierre Brouant, Said El Khyari, Joseph Molnár, Yves Barra, Jacques Barbe

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We studied the effect of thioacridine derivatives on the function of P-glycoprotein in MDR mouse T-lymphoma cell line L5178 and in MDR human leukemia cell line K562/ADR by rhodamine 123 uptake assay. The effect of some selected thioacridines was also investigated on the expression of the mdr1 gene. Expression was analysed by RT-PCR. Two compounds: 3-amino-9-thio-(4'-nitrobenzyl)acridinone and 2,7-dimethoxy-9-thio-(2'-diethlaminoethyl) acridinone were able to block the function of the P-gp, and also to decrease significantly mdr1 demonstrated gene expression. Because these two derivatives exert their positive simultaneously effects as reversing agents they could be potential candidate anticancer agents for further investigation. The thioacridines, which do not affect P-gp function, do not affect or increase the expression of mdr1 gene. Our results showed the structure-activity relationships of these compounds, providing a direction for the development of new, more active compounds.

Original languageEnglish
Pages (from-to)3053-3058
Number of pages6
JournalAnticancer research
Volume18
Issue number4 C
Publication statusPublished - Jul 1 1998

Keywords

  • P-glycoprotein
  • Thioacridines
  • mdr1 gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Hevér, A., Santelli-Rouvier, C., Brouant, P., El Khyari, S., Molnár, J., Barra, Y., & Barbe, J. (1998). Effect of new thioacridine derivatives on P-gp function and on mdr1 gene expression. Anticancer research, 18(4 C), 3053-3058.