Title:Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer
Volume: 15
Issue: 6
Author(s): Muthu K. Shanmugam, Sudha Warrier, Alan P. Kumar*, Gautam Sethi* Frank Arfuso
Affiliation:
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599,Singapore
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600,Singapore
Keywords:
Neovascularization, angiogenesis, hypoxia, angiopoietin, growth factor, vascular, natural products, bioactive compounds.
Abstract: Background: Neovascularization, also known as angiogenesis, is the process of capillary
sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal
embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the
body. Any disruption in this process can lead to the development of various chronic diseases, including
cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth
to malignant phenotypes and promoting metastasis. The leakiness in the tumor microvasculature is attributed
to the tumor cells migrating to distal site organs and forming colonies.
Methods: In this article, we briefly review the various mediators involved in the angiogenic process and
the anti-angiogenic potential of selected natural compounds against various malignancies.
Results: Several growth factors and their receptors such as vascular endothelial growth factor and receptor
(VEGF/VEGFR), basic fibroblast growth factor and receptor (bFGF/FGFR), angiopoietins, and hypoxia
inducible factors facilitate the development of angiogenesis and are attractive anti-cancer targets.
Natural products represent a rich diversity of compounds for drug discovery and are currently being
actively exploited to target tumor angiogenesis.
Conclusion: Agents such as curcumin, artemisinin, EGCG, resveratrol, emodin, celastrol, thymoquinone
and tocotrienols all have shown prominent anti-angiogenic effects in the preclinical models of
tumor angiogenesis. Several semi-synthetic derivatives and novel nano-formulations of these natural
compounds have also exhibited excellent anti-angiogenic activity by increasing bioavailability and delivering
the drugs to the sites of tumor angiogenesis.
