Carcinogenesis Advance Access published online on September 4, 2006
Carcinogenesis, doi:10.1093/carcin/bgl162
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1 Molecular Oncology Laboratory, National Institute for Cancer Research, Genova 16132, Italy
* To whom correspondence should be addressed. Several natural compounds, especially plant products and dietary constituents, are able to exhibit "angiopreventive" (anti-angiogenic chemoprevention) 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 inhibited in vivo angiogenesis and vascular tumor growth. In addition to Akt, the NF-
Received February 1, 2006
Revised July 25, 2006
Accepted August 13, 2006
CANCER PREVENTION
The Akt inhibitor deguelin, is an angiopreventive agent also acting on the NF-
Raffaella Dell'Eva 1, Claudia Ambrosini 1, Simona Minghelli 2, Douglas M. Noonan 3, Adriana Albini 1 *, and Nicoletta Ferrari 1
B pathway
2 Centro di Biotecnologie Avanzate, Genova 16132, Italy
3 Dept of Clinical and Biological Sciences, University of Insubria, Varese 21100, Italy
Adriana Albini, E-mail: adriana.albini{at}istge.it
Abstract 
B 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 TNF
. These findings reveal a new therapeutic potential for deguelin in angioprevention and anti-angiogenic therapy.
Note: R. Dell'Eva and C. Ambrosini contributed equally to this study.
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