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Anticancer Res. 2016 Jun;36(6):2751-8.

Antiproliferative Effects of Various Furanoacridones Isolated from Ruta graveolens on Human Breast Cancer Cell Lines.

Author information

1
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
2
Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
3
Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
4
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary zupko@pharm.u-szeged.hu.

Abstract

BACKGROUND/AIM:

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).

MATERIALS AND 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.

KEYWORDS:

Ruta graveolens L.; acridone alkaloids; antitumor effect; apoptosis; furanoacridones

PMID:
27272785
[Indexed for MEDLINE]

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