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. 2020 Feb 14;26(6):562–597. doi: 10.3748/wjg.v26.i6.562

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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

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Tumor necrosis factor from immune cells can activate nuclear factor-kappa B, a central activator that induces the expression of inflammatory genes, such as COX-2, tumor necrosis factor-alpha, inducible nitric oxide synthase, and ICAM-1, and tumor cell survival, proliferation, invasion, angiogenesis, and metastasis are affected when tumor necrosis factor binds to tumor necrosis factor receptor 1 and assembles with tumor necrosis factor receptor 1-associated death domain protein, tumor necrosis factor receptor-associated factor 2, cellular inhibitor of apoptosis protein 1 or 2, and linear ubiquitin chain assembly complex[219,230]. Similarly, another cytokine, interleukin (IL)-6, is also secreted in the tumor microenvironment. The binding of IL-6 to the IL-6 receptor activates STAT3, a major oncogenic transcription factor[229]. After binding to the IL-6 receptor at the cell surface, gp130 dimerization and activation and the transphosphorylation of JAKs are achieved and then contribute to the phosphorylation of STAT3, causing its translocation from the cytoplasm to the nucleus, where it modulates the expression of a variety of genes[229]. Tea polyphenols (TPs) can inhibit inflammatory gene expression caused by cytokines secreted by immune cells in colorectal cancer, with the suppression of COX-2 being particularly important. TPs can inhibit COX-2 in a multilevel process, majorly at the transcriptional and post-transcriptional level. In addition, (-)-epigallocatechin-3-gallate (EGCG) can suppress the expression of nuclear factor-kappa B (NF-κB) through interruption of folate cycle. EGCG can inhibit dihydrofolate reductase and thereby interfere with the folate cycle, causing the release of adenosine. Adenosine binding to specific receptors inhibits the activation of NF-κB. In addition, prostaglandin E2 (PGE2) can also activate COX-2 by stimulating EP receptor (EP1-4) signaling, with the subsequent induction of colorectal cancer onset. Moreover, TPs can inhibit the synthesis of PGE2 and thereby suppress the expression of COX-2. TNF: Tumor necrosis factor; TRADD: TNFR1-associated death domain protein; TRAF2: TNFR-associated factor 2; LUBAC: Linear ubiquitin chain assembly complex; IL-6: Interleukin 6; TP: Tea polyphenol.