Antitumour properties of acridone alkaloids on a murine lymphoma cell line.
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.
Réthy
Borbála
B
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
Hohmann
Judit
J
Minorics
Renáta
R
Varga
András
A
Ocsovszki
Imre
I
Molnár
Joseph
J
Juhász
Kata
K
Falkay
George
G
Zupkó
István
I
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D054831:Acridones / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects; D005434:Flow Cytometry; D007940:Leukemia L5178 / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D011419:Propidium; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020112:Rhodamine 123 / Q000493:pharmacokinetics; D013194:Staining and Labeling / Q000379:methods
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D054831:Acridones; D000470:Alkaloids; D017304:Annexin A5; D012333:RNA, Messenger; D020112:Rhodamine 123; D011419:Propidium