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Article Publish Status: FREE
Abstract Title:

Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation.

Abstract Source:

Oncotarget. 2016 Aug 1. Epub 2016 Aug 1. PMID: 27494895

Abstract Author(s):

Cristina Gallo, Katiuscia Dallaglio, Barbara Bassani, Teresa Rossi, Armando Rossello, Douglas M Noonan, Gabriele D'Uva, Antonino Bruno, Adriana Albini

Article Affiliation:

Cristina Gallo

Abstract:

Angiogenesis, a process characterized by the formation of new blood vessels from pre-existing ones, is a crucial step in tumor growth and dissemination. Recently, increased attention has been addressed to the ability of flavonoids to prevent cancer by suppressing angiogenesis, strategy that we named"angioprevention". Several natural compounds exert their anti-tumor properties by activating 5' adenosine monophosphate-activated protein kinase (AMPK), a key regulator of metabolism in cancer cells. Drugs with angiopreventive activities, in particular metformin, regulate AMPK in endothelial cells. Here we investigated the involvement of AMPK in the anti-angiogenic effects of xanthohumol (XN), the major prenylated flavonoid of the hop plant, and mechanisms of action. The anti-angiogenic activity of XN was more potent than epigallocatechin-3-gallate (EGCG). Treatment of endothelial cells with XN led to increased AMPK phosphorylation and activity. Functional studies using biochemical approaches confirmed that AMPK mediates XN anti-angiogenic activity. AMPK activation by XN was mediated by CAMMKβ, but not LKB1. Analysis of the downstream mechanisms showed that XN-induced AMPK activation reduced nitric oxide (NO) levels in endothelial cells by decreasing eNOS phosphorylation. Finally, AKT pathway was inactivated by XN as part of its anti-angiogenic activity, but independently from AMPK, suggesting that these two signaling pathways proceed autonomously. Our study dissects the molecular mechanism by which XN exerts its potent anti-angiogenic activity, pointing out AMPK as a crucial signal transducer.

Study Type : In Vitro Study

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Sayer Ji
Founder of GreenMedInfo.com

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500+ pages of Natural Medicine Alternatives and Information.

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