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Research ArticleExperimental Studies

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 and ISTVÁN ZUPKÓ
Anticancer Research September 2008, 28 (5A) 2737-2743;
BORBÁLA RÉTHY
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JUDIT HOHMANN
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RENÁTA MINORICS
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ANDRÁS VARGA
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IMRE OCSOVSZKI
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JOSEPH MOLNÁR
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KATA JUHÁSZ
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GEORGE FALKAY
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ISTVÁN ZUPKÓ
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  • For correspondence: zupko@pharm.u-szeged.hu
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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 L5178 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.

  • Furanoacridones
  • multidrug resistance
  • apoptosis
  • Received April 18, 2008.
  • Revision received June 19, 2008.
  • Accepted July 4, 2008.
  • Copyright© 2008 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 28 (5A)
Anticancer Research
Vol. 28, Issue 5A
September-October 2008
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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
Anticancer Research Sep 2008, 28 (5A) 2737-2743;

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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
Anticancer Research Sep 2008, 28 (5A) 2737-2743;
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