Shikimic acid promotes estrogen receptor(ER)-positive breast cancer cells proliferation via activation of NF-κB signaling

Toxicol Lett. 2019 Sep 15:312:65-71. doi: 10.1016/j.toxlet.2019.04.030. Epub 2019 Apr 29.

Abstract

Shikimic acid (SA), a widely-known hydroaromatic compound enriched in Bracken fern and Illicium verum (also known as Chinese star anise), increases the risk of gastric and esophageal carcinoma, nevertheless, the influence of SA on breast cancer remains indistinct. Herein we found that, with models in vitro, SA significantly promoted estrogen receptor(ER) positive cells proliferation and NF-κB activation was involved in it. Moreover, our data showed that IκBα, a critically endogenous inhibitor of NF-κB, was repressed. Subsequently, we found increase of miR-300 by SA treatment sand miR-300 could target IκBα mRNA. Additionally, inhibition of miR-300 abrogated the repression of IκBα by SA. As a result, miR-300 was also involved in NF-κB activation and breast cancer cells proliferation promotion due to SA exposure. Taken together, with ER-positive breast cancer cell models in vitro, MCF-7 and T47D, our results implied that SA promoted breast cancer cells proliferation via a miR-300-induced NF-κB dependent pathway controlling cell cycle proteins.

Keywords: ER-positive breast cancer; IκBα; NF-κB; SA.

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Cell Proliferation / drug effects*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Shikimic Acid / chemistry
  • Shikimic Acid / pharmacology*
  • Shikimic Acid / therapeutic use
  • Signal Transduction / drug effects

Substances

  • MIRN300 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Receptors, Estrogen
  • Shikimic Acid