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

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 proapoptotic effects on human breast cancer cell lines (MCF7, 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 mu M). 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 G(2)/M and G(0)/G(1) and increasing the S phase and the appearance of the subdiploid (sub-G(1)) 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.