Curcumin and Epigallocatechin-3-Gallate: Targeting Receptor Tyrosine Kinases and their Signaling Pathways in Cancer Therapy

Receptor tyrosine kinases (RTKs) are single-pass transmembrane receptors that play a key role as signal transducers. Abnormality of RTK has been revealed in a wide spectrum of cancers, providing appropriate targeted therapy. Treatment with common RTK inhibitors is associated with the challenge of resistance, which requires the use of other effective therapeutic agents. Phytochemicals can use or be combined with other therapeutic agents to improve cancer combating efficiency.

Curcumin and epigallocatechin-3-gallate are attractive natural ingredients usually due to their powerful anti-cancer functionality, wide spectrum of targets and low toxicity. Many studies conducted on cancer cells and animal models demonstrated that the inhibitory effects of curcumin and epigallocatechin-3-gallate on RTKs and their downstream signaling pathways reduced proliferation, angiogenesis and invasion in a variety of cancers. Among the many documented targets of curcumin and epigallocatechin-3-gallate, RTKs and their related ligands are one of the important suppressive targets of them.

This review focuses on the molecular mechanisms of curcumin and epigallocatechin-3-gallate targeting epidermal growth factor receptor, vascular endothelial growth factor and insulin receptor and their downstream signaling pathways like the PI3K/Akt/mTOR, Ras/ERK and NF-κB pathways.