Antitumour properties of acridone alkaloids on a murine lymphoma cell line

Borbála Réthy, Judit Hohmann, Renáta Minorics, András Varga, Imre Ocsovszki, Joseph Molnár, Kata Juhász, George Falkay, István Zupkó

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The aim of the present study was to investigate the anticancer properties of a set of furanoacridone alkaloids, arborinine and evoxanthine, including the inhibitory effect of P-glycoprotein (Pgp) and the apoptosis-inducing capacity. The tested alkaloids were evaluated for multidrug resistance (MDR)-reversing activity on human Pgp-transfected L5178 mouse lymphoma cells, using the rhodamine-123 (Rh-123) assay. The antiproliferative effects of natural compounds and their interactions with doxorubicin were determined in MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. Apoptosis-inducing activity was additionally measured by means of dual annexin V and propidium iodide staining. RT-PCR was used to test the expression of Pgp mRNA after acridone treatment. All of the acridones investigated increased the accumulation of Rh-123. Gravacridonetriol and gravacridonediol monomethyl ether increased the antiproliferative effect of doxorubicin on resistant L5I78 cells. Treatment with these agents resulted in a decrease in Pgp mRNA levels. Naturally occurring acridone alkaloids exhibit a beneficial combination of anticancer effects and, accordingly, the acridone skeleton can be considered useful in the design of novel antiproliferative agents.

Original languageEnglish
Pages (from-to)2737-2743
Number of pages7
JournalAnticancer research
Volume28
Issue number5 A
Publication statusPublished - Sep 1 2008

Keywords

  • Apoptosis
  • Furanoacridones
  • Multidrug resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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