Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600. Singapore.
Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal University, Bangalore-560 065. India.
Curr Vasc Pharmacol. 2017;15(6):503-519. doi: 10.2174/1570161115666170713094319.
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.
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.
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.
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.
新生血管形成,也称为血管生成,是毛细血管从现有血管中萌芽的过程。这个生理过程是正常胚胎发育的一个显著特征,因为血管通常为身体的细胞提供氧气和营养。这个过程的任何中断都可能导致各种慢性疾病的发展,包括癌症。在癌症中,异常的血管生成在维持肿瘤的持续生长、向恶性表型转化和促进转移方面起着突出的作用。肿瘤微血管的渗漏归因于肿瘤细胞迁移到远处的器官并形成菌落。
在本文中,我们简要回顾了参与血管生成过程的各种介质,以及选定的天然化合物对各种恶性肿瘤的抗血管生成潜力。
几种生长因子及其受体,如血管内皮生长因子和受体(VEGF/VEGFR)、碱性成纤维细胞生长因子和受体(bFGF/FGFR)、血管生成素和缺氧诱导因子,促进了血管生成的发展,是有吸引力的抗癌靶点。天然产物代表了丰富多样的化合物,可用于药物发现,目前正在积极开发以靶向肿瘤血管生成。
姜黄素、青蒿素、EGCG、白藜芦醇、大黄素、雷公藤红素、胸腺醌和生育三烯酚等药物在肿瘤血管生成的临床前模型中均表现出显著的抗血管生成作用。这些天然化合物的几种半合成衍生物和新型纳米制剂也通过增加生物利用度并将药物输送到肿瘤血管生成部位,表现出优异的抗血管生成活性。