The Akt inhibitor deguelin, is an angiopreventive agent also acting on the NF-κB pathway

Raffaella Dell'Eva, Simona Minghelli, Simona Minghelli, Douglas M. Noonan, Adriana Albini, Nicoletta Ferrari

Research output: Contribution to journalArticle

Abstract

Several natural compounds, especially plant products and dietary constituents, are able to exhibit 'angiopreventive' (anti-angio genic chemo prevention) activities both in vitro and in vivo. Deguelin is a rotenoid of the flavonoid family with chemopreventive activities able to decrease tumor incidence in animal models for lung, colon, mammary and skin carcinogenesis through Akt inhibition. Here we show that deguelin belongs to the 'angiopreventive' molecules and provide evidence for molecular events associated with its anti-angiogenic properties. The data show that deguelin inhibits HUVE cells growth by inducing cell-cycle arrest in the G0/G1 phase and in the absence of apoptosis. Growth arrest is associated with induction of p21 and p53 and decreased survivin levels. Deguelin also interferes with several points in the angiogenic process, including inhibition of endothelial cell migration, invasion and metalloprotease production, and potently inhibits in vivo angiogenesis and vascular tumor growth. In addition to Akt, the nuclear factor-kappaB (NF-κB) kinase pathway, which plays a critical role in the regulation of inflammation, vascular homeostasis and angiogenesis, was also repressed by deguelin even in the presence of inflammatory stimuli such as tumor necrosis factor-α (TNF-α). These findings reveal a new therapeutic potential for deguelin in angioprevention and anti-angiogenic therapy.

Original languageEnglish
Pages (from-to)404-413
Number of pages10
JournalCarcinogenesis
Volume28
Issue number2
DOIs
Publication statusPublished - Feb 2007

ASJC Scopus subject areas

  • Cancer Research

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