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Abstract Title:

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

Abstract Source:

Anticancer Res. 2016 Jun ;36(6):2751-8. PMID: 27272785

Abstract Author(s):

Zsuzsanna Schelz, Imre Ocsovszki, Noémi Bózsity, Judit Hohmann, István Zupkó

Article Affiliation:

Zsuzsanna Schelz

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)=2.27μM). 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 iodidestaining 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.

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