Cell cycle analysis and cytotoxic potential of Ruta graveolens against human tumor cell lines

There are reports on the presence of various compounds exerting different biological activities in Ruta graveolens, a plant of Rutaceae family. The aim of the present study was to evaluate in vitro cytotoxicity of the total extract of R. graveolens against tumor cell lines of different origin. Aerial parts of the plant was extracted with 70% ethanol by sonication method and cytotoxic activity was examined on RAJI, RAMOS, RPM18866, U937, jurkat, MDA-MB-453, MCF-7, LNCap-FGC-10, 5637, HeLa, SK-OV-3, A549, Mehr-80 and also peripheral blood mononuclear cells (PBMC) by the use of WST-1 assay. Results were expressed as IC50 values. R. graveolens extract showed high cytotoxic activity against RAJI and RA-MOS, two Burkitt's lymphoma cell lines, with an IC50 equal to 24.3 mu g/ml and 35.2 mu g/ml respectively and LNCap-FGC-10, a prostate adenocarcinoma cell line with an IC50 equal to 27.6 mu g/ml as well as Mehr-80, a newly established Large Cell Lung Carcinoma (IC50=46.2 mu g/ml). No significant anti-proliferative activity was observed on other cell lines including MCF-7, MDA-MB-453, SK-OV-3, HeLa, 5637, JURKAT and RPM18866. Adverse cytotoxic effect of R. graveolens was investigated against PBMCs and a significantly lower effect of this extract (IC50 = 104 mu g/ml) was seen on normal cells compared with RAJI and RAMOS, two haematopoietic cell lines (p<0.05). Flow cytometry analysis of R. graveolens extract for determining cell cycle distribution in RAJI cells demonstrated that its anti-proliferative effects is associated with a significant increase in sub-G1 population. These results indicate the presence of naturally occurring cytotoxic compound(s) in R. graveolens with probable apoptosis inducing capacity with low cytotoxicity on normal mononuclear cells.