Abstract:
In the ayurvedic system of medicine, themedicinal plant, Withania somnifera Dunal(Solanaceae) finds application for numerousailments including cancer. This herbal plant yieldsa host of steroidal lactones called withanolides,some of which have shown growth inhibition ofhuman tumor cell lines. Withaferin A amongstthese withanolides reportedly is very active inimpairing antitumor activity. However; theunderlying molecular mechanisms of this activityremains still unclear. In the present study, we haveshown that withaferin A inhibited vascularendothelial cell growth factor (VEGF) -inducedtube formation by human umbilical vein endothelialcells (HUVECs) and angiogenesis in chickchorioallantoic membrane (CAM) assay. InEhrlich ascites tumor (EAT) model, the animalstreated with withaferin A suppressed in vivo, theperitoneal angiogenesis and microvessel density.When compared to the untreated animals, thewithaferin A treated tumor bearing mice showeda decrease in the volume of ascites and tumorcell number. Quantitation of VEGF levels in ascitesfrom withaferin A untreated or treated tumorbearing mice indicated decreased secretion ofVEGF in ascites from treated mice, as measuredby ELISA. Studies at molecular level revealedthat withaferin A inhibits binding of Sp1transcription factor to VEGF-gene promoter, in order to exert its antiangiogenic activity. Theseresults clearly indicate the antiangiogenic potentialof withaferin A in modulating antitumor activity.