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Current Trends in Biotechnology and Pharmacy
Year : 2009, Volume : 3, Issue : 2
First page : ( 138) Last page : ( 148)
Print ISSN : 0973-8916. Online ISSN : 2230-7303.

Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription factor

Prasanna Kumar S., Shilpa P., Salimath Bharathi P. *

Department of Studies in Biotechnology, University of Mysore, Manasagangotri, Mysore-570006, Karnataka, India.

For Correspondent: Salimathuom@rediffmail.com

Abstract

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.

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Keywords

Ehrlich ascites tumor, Withaferin A, Angiogenesis, Sp1, VEGF.

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