Current Trends in Biotechnology and Pharmacy

In the ayurvedic system of medicine, the medicinal plant, Withania somnifera Dunal (Solanaceae) finds application for numerous ailments including cancer. This herbal plant yields a host of steroidal lactones called withanolides, some of which have shown growth inhibition of human tumor cell lines. Withaferin A amongst these withanolides reportedly is very active in impairing antitumor activity. However; the underlying molecular mechanisms of this activity remains still unclear. In the present study, we have shown that withaferin A inhibited vascular endothelial cell growth factor (VEGF) -induced tube formation by human umbilical vein endothelial cells (HUVECs) and angiogenesis in chick chorioallantoic membrane (CAM) assay. In Ehrlich ascites tumor (EAT) model, the animals treated with withaferin A suppressed in vivo, the peritoneal angiogenesis and microvessel density. When compared to the untreated animals, the withaferin A treated tumor bearing mice showed a decrease in the volume of ascites and tumor cell number. Quantitation of VEGF levels in ascites from withaferin A untreated or treated tumor bearing mice indicated decreased secretion of VEGF in ascites from treated mice, as measured by ELISA. Studies at molecular level revealed that withaferin A inhibits binding of Sp1 transcription factor to VEGF-gene promoter, in order to exert its antiangiogenic activity. These results clearly indicate the antiangiogenic potential of withaferin A in modulating antitumor activity.