Abstract
BackgroundReceptor tyrosine kinases (RTKs) are single-pass transmembrane proteins that play significant roles in regulating cellular processes, including cell division and growth. Overexpression and mutations of RTKs have been found in clinical manifestations of different forms of cancer. Therefore, RTKs have received considerable interest as a therapeutic biomarker in the treatment of cancer cells.Main body of the abstractComprehensive data on RTKs, pharmacological and biological properties of natural compounds were systematically searched up to 2021 using relevant keywords from various databases, such as Google Scholar, PubMed, Web of Science, and Scopus. The scientific search by various standard electronic resources and databases unveils the effectiveness of medicinal plants in the treatment of various cancers. In vitro and in vivo studies suggested that bioactive compounds such as flavonoids, phenols, alkaloids, and many others can be used pharmacologically as RTKs inhibitors (RTKI) either by competing with ATP at the ATP binding site of the tyrosine kinase domain or competing for the receptor extracellular domain. Additionally, studies conducted on animal models indicated that inhibition of RTKs catalytic activity by natural compounds is one of the most effective ways to block the activation of RTKs signaling cascades, thereby hampering the proliferation of cancer cells. Furthermore, various pharmacological experiments, transcriptomic, and proteomic data also reported that cancer cells treated with different plants extracts or isolated phytochemicals exhibited better anticancer properties with minimal side effects than synthetic drugs. Clinically, natural compounds have demonstrated significant anti-proliferative effect via induction of cell apoptosis in cancer cell lines.Short conclusionAn in-depth knowledge of the mechanism of inhibition and structural characterization of RTKs is important to the design of novel and selective RTKIs. This review focuses on the molecular mechanisms and structures of natural compounds RTKI targeting vascular endothelial growth factor, epidermal growth factor receptor, insulin receptor, and platelet-derived growth factor while also giving future directions to ameliorate the scientific burden of cancer.Graphic abstract
Highlights
Receptor tyrosine kinases Receptor tyrosine kinases (RTKs) are membrane proteins that aid cell communication with their extracellular milieu, thereby playing a pivotal role in signal transduction, cellular processes, and pathogenesis of different cancer cells
This review focuses on the molecular mechanisms and structures of natural compounds RTKs inhibitors (RTKI) targeting vascular endothelial growth factor, epidermal growth factor receptor, insulin receptor, and platelet-derived growth factor while giving future directions to ameliorate the scientific burden of cancer
Natural compounds have substantially been characterized as a secondary metabolite of plants, demonstrating biological and pharmacological properties in preventing the progression of tumors and adjunct cancer therapy
Summary
The use of chemotherapeutics has been buoyed by the need to stop rapidly dividing cells in the management of tumors via the activation of apoptotic factors and muddling of the cell cycle, inhibiting mitosis. Balogun et al Futur J Pharm Sci (2021) 7:197 specificity against cancerous cells while posing a considerable amount of damage on uninfected/beneficial myelocytes or gametocytes [1, 2] This worry has been subdued by the emergence of small molecule kinase inhibitors, characterized by their specificity and selectivity, downregulation of oncogenesis activation proteins, and making their receptor unavailable for binding [3, 4]. Due to the obdurate property of cancerous cells, coupled with the worrisome adverse responses caused by chemotherapeutic agents to the immune system, the use of natural compounds could be the nostrum in overcoming this barrier. Natural compounds such as flavonoids, terpenoids, polyphenols, and alkaloids have increasingly attracted attention as studies have revealed their anticancer, antioxidant, and cardio-protective activity over time. Novel devices capable of linking structure–biological function activity of natural compounds in a targeted manner are, advised to be worked upon
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