Background:
Cancer is a complex disease involving genetic and epigenetic alteration
that allows cells to escape normal homeostasis. Kinases play a crucial role in signaling pathways
that regulate cell functions. Deregulation of kinases leads to a variety of pathological changes, activating
cancer cell proliferation and metastases. The molecular mechanism of cancer is complex
and the dysregulation of tyrosine kinases like Anaplastic Lymphoma Kinase (ALK), Bcr-Abl (Fusion
gene found in patient with Chronic Myelogenous Leukemia (CML), JAK (Janus Activated
Kinase), Src Family Kinases (SFKs), ALK (Anaplastic lymphoma Kinase), c-MET (Mesenchymal-
Epithelial Transition), EGFR (Epidermal Growth Factor receptor), PDGFR (Platelet-Derived
Growth Factor Receptor), RET (Rearranged during Transfection) and VEGFR (Vascular Endothelial
Growth Factor Receptor) plays major role in the process of carcinogenesis. Recently, kinase
inhibitors have overcome many problems of traditional cancer chemotherapy as they effectively
separate out normal, non-cancer cells as well as rapidly multiplying cancer cells.
Methods:
Electronic databases were searched to explore the small molecule tyrosine kinases by
polyphenols with the help of docking study (Glide-7.6 program interfaced with Maestro-v11.3 of
Schrödinger 2017) to show the binding energies of polyphenols inhibitor with different tyrosine
kinases in order to differentiate between the targets.
Results:
From the literature survey, it was observed that the number of polyphenols derived from
natural sources alters the expression and signaling cascade of tyrosine kinase in various tumor
models. Therefore, the development of polyphenols as a tyrosine kinase inhibitor against targeted
proteins is regarded as an upcoming trend for chemoprevention.
Conclusion:
In this review, we have discussed the role of polyphenols as chemoreceptive which
will help in future for the development and discovery of novel semisynthetic anticancer agents
coupled with polyphenols.
Acid sphingomyelinase is required for cell surface presentation of Met receptor tyrosine kinase in cancer cells
