Anticancer Molecular Mechanisms of Epigallocatechin Gallate: An Updated Review on Clinical Trials

Human physiology is a complex process encompassing various biochemical mechanisms, regulated by hundreds of chemical mediators, thus making it more complicated to understand. Balance between these mediators is mandatory to continue the helm of life; however, an imbalance can disrupt normal physiological functions and lead to chronic health conditions. Cancer is one such chronic state that occurs due to an imbalance or overproduction of reactive oxygen and nitrogen species (RONS), which are highly unstable and damage other chemical constituents in the body. The mutilation at the cellular level results in DNA and genetic mutation, uncontrolled cell proliferation, metastasis, organ dysfunction, and ultimately mortality. Various types of cancers are intimidating human life globally, and lung cancer is leading them all, followed by breast and colorectal cancer. Oxidative stress (OS) is the main root cause of cancers that occur due to overproduced RONS. Tumor suppressor genes (TSGs) like p53, PTEN, INK4, MADR2, APC, and oncogenes such as HER2, BCR/ABL1, CMYC, EML4AK, RAS, WNT, ERK, and TRK get mutated by OS. Moreover, various pro-inflammatory markers i.e., IL-1, IL-6, TNF-α, IFN-γ, TGF-β and growth factors (VEGF, EGF, IGF-2) are also involved in cancer progression. Along with these aspects, the oncogenesis involves different signaling pathways/axis such as MAPK, PI3K, mTOR, Wnt/β-catenin, GSK3, and NF-κB. Epigallocatechin gallate (EGCG), a bioactive compound abundantly existing in green tea and grapes with strong antioxidant activity and anticancer potential, is a suitable approach to reduce the cancer burden. The in vitro and in vivo anticancer studies of EGCG proved anticancer and anti-tumor effects through modulation of cancer signaling pathways, reduction in cell proliferation, decreased metastasis, suppressed angiogenesis, enhanced antioxidant activity, inhibited pro-inflammatory biomarkers, improved TSGs expression, and downregulated oncogenes expression. Shortly, the current review focuses on the anticancer potential of EGCG through possible mechanisms.