Angiogenesis and cancer prevention: a vision

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Solid tumor growth and dissemination are critically dependent on angiogenesis.
• Inflammation is increasingly recognized as a key driver of tumor angiogenesis.
• Chemopreventive molecules often target angiogenesis, a concept termed angioprevention.

Purpose of the Study:

• To investigate the anti-angiogenic mechanisms of various chemopreventive molecules.
• To explore the role of inflammation in tumor angiogenesis and its modulation by these agents.
• To analyze gene expression changes induced by these molecules in endothelial cells.

Main Methods:

• In vivo Matrigel sponge angiogenic assay.
• Inhibition of Kaposi's sarcoma tumor cell growth in nude mice.
• Functional genomics and gene expression analysis using Affymetrix GeneChip arrays in human umbilical endothelial cells (HUVEC).

Main Results:

• N-acetyl-cysteine (NAC), epigallocatechin-3-gallate (EGCG), Xanthohumol, and 4-hydroxyfenretinide (4HPR) demonstrated anti-angiogenic effects.
• NAC and flavonoids suppressed the IkB/NF-kappaB signaling pathway, reducing NF-kappaB target gene expression.
• Antioxidants induced selective apoptosis in transformed cells by downregulating NF-kappaB-dependent survival factors.

Conclusions:

• Chemopreventive molecules inhibit angiogenesis by targeting endothelial cell activation and innate immunity.
• Repression of the NF-kappaB pathway by antioxidants suggests anti-inflammatory effects contributing to angiogenesis inhibition.
• These angiopreventive agents modulate inflammatory cell recruitment and activation, linking inflammation and vascularization to cancer progression.