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Publication : Tocopherols inhibit esophageal carcinogenesis through attenuating NF-κB activation and CXCR3-mediated inflammation.

First Author  Yang H Year  2018
Journal  Oncogene Volume  37
Issue  29 Pages  3909-3923
PubMed ID  29662196 Mgi Jnum  J:264024
Mgi Id  MGI:6193021 Doi  10.1038/s41388-018-0246-8
Citation  Yang H, et al. (2018) Tocopherols inhibit esophageal carcinogenesis through attenuating NF-kappaB activation and CXCR3-mediated inflammation. Oncogene 37(29):3909-3923
abstractText  Esophageal cancer is one of the common causes of cancer mortality in the world. The predominant histological subtype, esophageal squamous cell carcinoma (ESCC), often results in poor prognosis due to the lack of effective approaches for the early diagnosis and treatment, highlighting the need for preventive intervention against this disease. Here we report that dietary tocopherols significantly prevents esophageal carcinogenesis by inhibiting the activation of NF-kappaB and the subsequent interaction of chemokine CXCL9/10/11 with their receptor CXCR3 in ESCC induced by N-nitrosomethylbenzylamine (NMBA) in murine models. Dietary supplementation with 0.15% alpha-tocopherol (alpha-T), delta-tocopherol (delta-T), or gamma-tocopherol rich mixture (gamma-TmT) markedly suppressed the production of pro-inflammatory cytokines, as well as the induction of CXCR3+ effector T cells (CD4+ Th1 and CD8+ CTLs) infiltration, especially at the early stage of carcinogenesis. In experiments in vivo and in vitro, these events were tightly correlated with the blockade of NF-kappaB activation. Our results show that tocopherols decrease carcinogenesis through inhibiting NF-kappaB and CXCR3 signaling, as well as related inflammation in early premalignant lesions. This pathway may offer a novel target for chemoprevention of esophageal cancer.
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