Artabotryside A, a constituent from Descurainia sophia (L.) induces cell death in U87 glioma cells through apoptosis and cell cycle arrest at G2/M phase

摘要

Descurainia sophia?(L.) commonly known as Webb ex Prantl (flixweed) is a Chinese traditional medicinal plant. Seeds of flixweed are used in the treatment of some cancers. However, the anticancer constituents from the seeds have not been investigated. The present study was aimed to identify bioactive compound with anti-glioma activity from the seeds of?D. sophia?(L.) and to examine the growth inhibitory effect on U87 glioblastoma cells and possible mechanism of action. From bioactive fraction, a flavonol glycoside, artabotryside A, has been isolated and evaluated for?in vitro?cytotoxicity against U87 glioma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead assay. Cellular and nuclear morphological changes were observed by phase contrast and fluorescence microscopy, respectively. Cell cycle analysis, apoptotic rate, mitochondrial membrane potential and level of reactive oxygen species (ROS) were detected by flow cytometry. Our results demonstrated that artabotryside A significantly reduced the proliferation of U87 cells in a dose- and time- dependent manner. By flow cytometric analysis, we found that artabotryside A treatment resulted in an increased apoptosis, mitotic arrest, level of ROS and decreased mitochondrial membrane potential in U87 cells in a time-dependent manner. Furthermore, caspase-3 inhibitor, Ac-DEVD-CHO, significantly inhibited the apoptotic effect of artabotryside A, indicating that artabotryside A induced caspase-dependent apoptosis in U87 cells. In addition, artabotryside A is less toxic to normal mouse splenocytes and glial cells. This selective cytotoxicity of artabotryside A against U87 glioma cells as compared to mouse splenocytes and glial cells is advantageous. Thus, artabotryside A might be a safe candidate for prevention and treatment of gliomas.