10-Hydroxy-2-decenoic acid inhibiting the proliferation of fibroblast-like synoviocytes by PI3K-AKT pathway

Int Immunopharmacol. 2015 Sep;28(1):97-104. doi: 10.1016/j.intimp.2015.05.036. Epub 2015 Jun 4.

Abstract

To reveal the mechanism of 10H2DA inhibiting the proliferation of fibroblast-like synoviocytes (FLSs) of RA patients. Cell proliferation, HDAC activity and histone acetylation level of FLS cells treated with 10H2DA were detected by MTT assay, Colorimetric HDAC Activity Assay and Western-blot. Different genes in FLS cells from RA patients were primary cultured and treated with 10H2DA. They were then screened by Human Transcriptome 1.0 ST microarrays and verified by real-time PCR. The results showed dose-dependent and time-dependent decreases in cell viability and HDAC activity in FLSs treated with 10H2DA, and time-dependent induction in the acetylation of H3 and H4 at the same time. 697 different genes were identified by HTA 1.0. The expressions of 7 target genes of the PI3K-AKT pathway were decreased and 4 target genes of cytokine-cytokine receptor interaction were increased verified by real-time PCR. These results imply that 10H2DA is a potential HDACI which inhibits the proliferation of FLS cells by PI3K-AKT pathway.

Keywords: 10H2DA; HDACIs; Microarray; PI3K–AKT pathway; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Arthritis, Rheumatoid / pathology
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Fatty Acids, Monounsaturated / pharmacology*
  • Fibroblasts / drug effects*
  • Gene Expression / drug effects
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Oncogene Protein v-akt / drug effects*
  • Phosphatidylinositol 3-Kinases / drug effects*
  • Primary Cell Culture
  • Receptors, Cytokine / drug effects
  • Receptors, Cytokine / genetics
  • Signal Transduction / drug effects*
  • Synovial Fluid / cytology*
  • Synovial Fluid / drug effects*

Substances

  • Cytokines
  • Fatty Acids, Monounsaturated
  • Histones
  • Receptors, Cytokine
  • 10-hydroxy-2-decenoic acid
  • Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt
  • Histone Deacetylases