Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells

Cancer Lett. 2014 Nov 28;354(2):407-16. doi: 10.1016/j.canlet.2014.08.011. Epub 2014 Aug 13.

Abstract

Pancreatic cancer is an aggressive malignancy and unresponsive to conventional chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis through inhibition of STAT3 and activation of p53 signaling pathways. Embelin substantially reduced the tumorigenicity of pancreatic cancer cells in vivo, which was associated with reduced inflammatory cells and immune suppressive cells, IL-17A(+) Th17, GM-CSF(+) Th, MDSCs and Treg, through inhibition of IL-6 secretion. Moreover, embelin decrease IL-6-induced STAT3 phosphorylation. In summary, embelin represents a novel therapeutic drug candidate for the clinical treatment of pancreatic cancer.

Keywords: Embelin; IL-6; Inflammation; MDSCs; Pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Benzoquinones / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Disease Progression
  • Down-Regulation
  • Female
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-6 / immunology*
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / pathology
  • STAT3 Transcription Factor / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Benzoquinones
  • Interleukin-6
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tumor Suppressor Protein p53
  • embelin