Gallic acid inhibits bladder cancer cell proliferation and migration via regulating fatty acid synthase (FAS)

J Food Drug Anal. 2018 Apr;26(2):620-627. doi: 10.1016/j.jfda.2017.06.006. Epub 2017 Jul 8.

Abstract

Bladder cancer is known as the world's ninth most prevalent cancer in 2012. New cytotoxic drugs have created considerable progress in the treatment. Gallic acid (GA) has been shown to inhibit carcinogenesis in animal models and various cancer cell lines. The aim of the present study was to evaluate the effect of GA on proliferation and migration inhibition of a bladder cancer cell line. The results showed that GA inhibited fatty acid synthase (FAS) activity and increased ER alpha level of TSGH-8301 bladder cancer cell. GA regulated the cell proliferation via the PI3K/AKT and MAPK/ERK pathway. Immunoprecipitation assay demonstrated that GA decreased Skp2 protein level and attenuated Skp2-p27 association. It was suggested that GA acted upstream of the proteasome to control p27 levels and ultimately inhibited G2/M phase transition. Further, transwell chambers assay showed that GA suppressed bladder cancer cell invasion and migration through p-AKT/MMP-2 signaling pathway. The finding indicated that GA inhibited TSGH-8301 bladder cancer cell growth, invasion and migration through inhibition of fatty acid synthase.

Keywords: Bladder cancer; Fatty acid synthase (FAS); Gallic acid; Migration; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acid Synthases / antagonists & inhibitors*
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Gallic Acid / pharmacology*
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Urinary Bladder Neoplasms / enzymology
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / physiopathology*

Substances

  • Enzyme Inhibitors
  • Gallic Acid
  • Fatty Acid Synthases
  • Phosphatidylinositol 3-Kinases
  • Matrix Metalloproteinase 2

Grants and funding

This investigation was supported by the Chung Shan Medical University and Cheng-Ching Hospital (CCGH-CSMU-104-001).