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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01002

Apigenin inhibits IL-6 transcription and suppresses esophageal carcinogenesis

 Bing-Hua Jiang1*, Jian-Ge Qiu2, Lin Wang2, Wen-Jing Liu2, Ju-Feng Wang2, Er-Jiang Zhao2, Feng-Mei Zhou2, Xiang-Bo Ji2, Li-Hong Wang2, Zhong-Kun Xia2, Wei Wang2, Marie Chia-mi Lin2, Ling-Zhi Liu1 and Ying-Xue Huang2
  • 1The University of Iowa, United States
  • 2Zhengzhou University, China

Esophagus cancer is the seventh causes of cancer-related deaths globally. In this study, we analyzed IL-6 gene expression in human esophagus cancer patients, and showed that IL-6 mRNA levels are significantly higher in tumor tissues and negatively correlated with overall survival, suggesting that IL-6 is a potential therapeutic target for esophagus cancer. We further demonstrated that apigenin, a nature flavone product of green plants, inhibited IL-6 transcription and gene expression in human esophagus cancer Eca-109 and Kyse-30 cells. Apigenin significantly and dose-dependently inhibited cell proliferation, and promoted apoptosis while stimulating the cleaved PARP (C-PARP) and Caspase-8 expression. It suppressed VEGF expression, and tumor-induced angiogenesis. Pretreatment of cells with IL-6 could completely reverse apigenin induced cellular changes. Finally, using a preclinical nude mice model subcutaneously xenografted with Eca-109 cells, we demonstrated the in vivo anti-tumor activity and mechanisms of apigenin. Taken together, this study revealed for the first time that apigenin is a new IL-6 transcription inhibitor, and that inhibiting IL-6 transcription is one of the mechanisms by which apigenin exhibits its anti-cancer effects. The potential clinical applications of apigenin in treating esophagus cancer warrant further investigations.

Keywords: Apigenin, esophagus cancer, IL-6, Tumor growth, inhibition

Received: 24 May 2019; Accepted: 06 Aug 2019.

Copyright: © 2019 Jiang, Qiu, Wang, Liu, Wang, Zhao, Zhou, Ji, Wang, Xia, Wang, Lin, Liu and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Bing-Hua Jiang, The University of Iowa, Iowa City, United States, bhjiang@zzu.edu.cn