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 RÉTHY, BORBÁLA
A1 HOHMANN, JUDIT
A1 MINORICS, RENÁTA
A1 VARGA, ANDRÁS
A1 OCSOVSZKI, IMRE
A1 MOLNÁR, JOSEPH
A1 JUHÁSZ, KATA
A1 FALKAY, GEORGE
A1 ZUPKÓ, ISTVÁN
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.