Frontiers in Pharmacology (Sep 2019)

Apigenin Inhibits IL-6 Transcription and Suppresses Esophageal Carcinogenesis

  • Jian-Ge Qiu,
  • Lin Wang,
  • Wen-Jing Liu,
  • Ju-Feng Wang,
  • Er-Jiang Zhao,
  • Feng-Mei Zhou,
  • Xiang-Bo Ji,
  • Li-Hong Wang,
  • Zhong-Kun Xia,
  • Wei Wang,
  • Marie Chia-mi Lin,
  • Ling-Zhi Liu,
  • Ying-Xue Huang,
  • Bing-Hua Jiang,
  • Bing-Hua Jiang

DOI
https://doi.org/10.3389/fphar.2019.01002
Journal volume & issue
Vol. 10

Abstract

Read online

Esophagus cancer is the seventh cause of cancer-related deaths globally. In this study, we analyzed interleukin 6 (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 (poly ADP-ribose polymerase) (C-PARP) and caspase-8 expression. It suppressed VEGF (Vascular endothelial growth Factor) 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 antitumor 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 anticancer effects. The potential clinical applications of apigenin in treating esophagus cancer warrant further investigations.

Keywords