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

Hui Yang, Miao Xu, Fang Lu, Qiannan Zhang, Yongquan Feng, Chung Yang, Ning Li, Xudong Jia

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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-κB 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% α-tocopherol (α-T), δ-tocopherol (δ-T), or γ-tocopherol rich mixture (γ-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-κB activation. Our results show that tocopherols decrease carcinogenesis through inhibiting NF-κB and CXCR3 signaling, as well as related inflammation in early premalignant lesions. This pathway may offer a novel target for chemoprevention of esophageal cancer.

Original languageEnglish (US)
Pages (from-to)3909-3923
Number of pages15
JournalOncogene
Volume37
Issue number29
DOIs
StatePublished - Jul 19 2018

Fingerprint

Tocopherols
Carcinogenesis
Inflammation
nitrosobenzylmethylamine
Esophageal Neoplasms
Chemokine CXCL9
CXCR3 Receptors
Chemoprevention
Dietary Supplements
Early Diagnosis
Cytokines
T-Lymphocytes
Mortality
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yang, Hui ; Xu, Miao ; Lu, Fang ; Zhang, Qiannan ; Feng, Yongquan ; Yang, Chung ; Li, Ning ; Jia, Xudong. / Tocopherols inhibit esophageal carcinogenesis through attenuating NF-κB activation and CXCR3-mediated inflammation. In: Oncogene. 2018 ; Vol. 37, No. 29. pp. 3909-3923.
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abstract = "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-κB 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{\%} α-tocopherol (α-T), δ-tocopherol (δ-T), or γ-tocopherol rich mixture (γ-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-κB activation. Our results show that tocopherols decrease carcinogenesis through inhibiting NF-κB 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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Tocopherols inhibit esophageal carcinogenesis through attenuating NF-κB activation and CXCR3-mediated inflammation. / Yang, Hui; Xu, Miao; Lu, Fang; Zhang, Qiannan; Feng, Yongquan; Yang, Chung; Li, Ning; Jia, Xudong.

In: Oncogene, Vol. 37, No. 29, 19.07.2018, p. 3909-3923.

Research output: Contribution to journalArticle

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