Antiproliferative Effects of Various Furanoacridones Isolated from Ruta graveolens on Human Breast Cancer Cell Lines.
OBJECTIVE
Thanks to its biologically active constituents, Ruta graveolens L. (Rutaceae) is a widely used medicinal plant. In our study, six furanoacridone alkaloids isolated from Ruta graveolens were investigated for their antiproliferative and pro-apoptotic effects on human breast cancer cell lines (MCF-7, MDA-MB-361, MDA-MB-231 and T47D).


METHODS
The cell lines were pretreated with alkaloid components (rutacridone, isogravacridone chlorine (IGC), gravacridonediol monomethyl ether, gravacridonediol, gravacridonetriol, a 1:1 mixture of gravacridonetriol and - diol monoglucosides) and their antiproliferative effects were determined by the MTT assay.


RESULTS
IGC had the most marked effect on cell proliferation of MDA-MB-231 (half maximal inhibitory concentration (IC50)=2.27 μM). Cell-cycle analysis was applied to quantify the effect of IGC on subpopulations of MDA-MB-231 and MCF-7 cells. It caused a cell-cycle disturbance by decreasing the G2/M and G0/G1 and increasing the S phase and the appearance of the subdiploid (sub-G1) population. Hoechst 33258-propidium iodide staining was used to evaluate the morphological changes in IGC-pretreated MDA-MB-231 and MCF-7 cells, revealing the appearance of apoptotic features. IGC was found to cause a modest activation of caspase-3 and -9, but not caspase-8, indicating the activation of an intrinsic apoptotic pathway in MDA-MB-231 cells.


CONCLUSIONS
These in vitro findings indicate that furanoacridones are suitable candidates for anticancer drug development.
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Zsuzsanna
Z
Schelz
Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Imre
I
Ocsovszki
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Noémi
N
Bózsity
Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Judit
J
Hohmann
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary zupko@pharm.u-szeged.hu.
István
I
Zupkó
D054831:Acridones / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D032105:Ruta / Q000737:chemistry*
D054831:Acridones; D000972:Antineoplastic Agents, Phytogenic; C041300:acridone; D020169:Caspases
Ruta graveolens L.; acridone alkaloids; antitumor effect; apoptosis; furanoacridones