Angiogenesis is the process by which new blood vessels are created from existing endothelial cells. Vascular endothelial growth factor (VEGF) is the primary regulator of endothelial cells (ECs), which are the biological components of freshly created capillaries. The drugs currently available are synthetic or humanised monoclonal antibodies, which are toxic and expensive. Natural therapies and compounds originating from plants, aquatic animals, and microbes are already being used to enhance conventional treatment for a variety of angiogenic illnesses, including cancer. The EGF, VEGF receptor, protein kinases, cyclooxygenase-2, HER2/neu gene, Bcl-2, coagulation pathways and nuclear factor kappa-B are among the molecular pathways addressed by natural products. Plant substances like spices, vegetables, fruits, and medicinal plants have anticancer activities. The current state of knowledge on tumor angiogenesis' molecular targets and the active compounds from natural sources that have been shown to inhibit cancer angiogenesis.
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Cancer has the potential to spread to nearby or distant organs. Blood or lymphatic vessels allow tumor cells to pass through, which allows them to travel through the intravascular stream and subsequently multiply at a different location (Nishida et al., 2006). Thus, the method through which cancer spreads to other tissues and organs, known as metastasis, renders this condition potentially fatal. A new blood vessel network must develop for metastasis to occur (Gutschner & Diederichs, 2012). The process of generating fresh blood vessels from already existing ones to meet cellular requirements is known as angiogenesis. Unquestionably, angiogenesis contributes to several (specific) physiological functions, including wound healing, diabetes, and the pathological processes of tumor growth and metastasis (Hoseinkhani et al., 2020). Neovascularization, also known as angiogenesis, is a complicated process that involves the activation, adhesion, proliferation, and transmigration of endothelial cells from already-existing blood arteries. Endothelial cells are the main actors in this process (M. K. Gupta & Qin, 2003). Endothelial cell turnover and angiogenesis occur somewhat slowly in a healthy adult organism (between three months and a year). Angiogenesis is only activated for a brief, defined period of time under specific circumstances, such as during embryogenesis, in the female reproductive system (for example, during the creation of the corpus luteum), or in wound healing. Cell adhesion molecules, growth factors, and certain signalling pathways work together to regulate angiogenesis (Paper, n.d.-a).
Tumor development is significantly influenced by angiogenesis because it provides nutrients and oxygen to malignant cells. Tumor cells secrete different growth factors, and this causes EC to produce new capillaries. Restricting the development of new blood vessel networks reduces metastasis and tumor size. Since angiogenesis is required for the growth of tumors, it is regarded as a potent target to decrease tumor development and spread. Actin, microtubules, methionine amino peptidase (MetAP), vascular endothelial growth factor (VEGFR)-related kinases, matrix metalloproteinase (MMPs), and histone deacetylases (HDACs) are among the target proteins that have been identified as being essential for angiogenesis (Wang & Miao, 2013). Metastasis and tumour size are reduced by limiting the development of new blood vessel networks. Antiangiogenesis is recognised as a potent therapy to lessen tumour development and spread because angiogenesis is essential for the formation of cancers. Anti-angiogenic chemicals, also known as angiogenesis inhibitors, are molecules or drugs that stop the flow of blood (Report, 2009). However, the majority of antiangiogenic (angiostatic) substances currently in use are humanized monoclonal antibodies or synthetic compounds that either target tyrosine kinases or angiogenic factors involved in the control of angiogenic pathways (Al-Husein et al., 2012). Although FDA approved medications like bevacizumab, ramucirumab etc., have showed promise effect on angiogenesis, their high price, substantial systemic toxicities, and the emergence of resistance make it necessary to find alternative, more potent anti-angiogenic compounds that are less expensive, have fewer, or even no side effects (Lu et al., 2016). However, it is important to remember that the current range of such drugs is substantially more constrained than the hypothetical therapeutic angiogenesis possibilities. According to the recent research natural substances also have angiogenesis-modulating effects (Sagar et al., 2006). Plant-based natural compounds are a wide range of molecules that occur in natural sources like spices, vegetables, fruits, and medicinal herbs that have anticancer activities. The state of knowledge at the moment on tumor angiogenesis' molecular targets and the pharmaceuticals produced from natural sources that have been proven to inhibit cancer angiogenesis. Therefore, the importance of natural compounds produced from plants, marine creatures, and microbes as an anti-angiogenic agent has been explored in this book chapter.