RT Journal Article SR Electronic T1 Antitumour Properties of Acridone Alkaloids on a Murine Lymphoma Cell Line JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2737 OP 2743 VO 28 IS 5A A1 BORBÁLA RÉTHY A1 JUDIT HOHMANN A1 RENÁTA MINORICS A1 ANDRÁS VARGA A1 IMRE OCSOVSZKI A1 JOSEPH MOLNÁR A1 KATA JUHÁSZ A1 GEORGE FALKAY A1 ISTVÁN ZUPKÓ YR 2008 UL http://ar.iiarjournals.org/content/28/5A/2737.abstract AB 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.