CXC195 suppresses proliferation and inflammatory response in LPS-induced human hepatocellular carcinoma cells via regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway

Biochem Biophys Res Commun. 2015 Jan 2;456(1):373-9. doi: 10.1016/j.bbrc.2014.11.090. Epub 2014 Dec 2.

Abstract

CXC195 showed strong protective effects in neuronal apoptosis by exerting its antioxidant activity. However, the anti-cancer effects of CXC195 is still with limited acquaintance. Here, we investigated the role of CXC195 in lipopolysaccharide (LPS)-induced human hepatocellular carcinoma (HCC) cells lines (HepG2) and the possible signaling pathways. CXC195 exhibited significant anti-proliferative effect and induced cell cycle arrest in LPS-induced HepG2 cells. In addition, CXC195 suppressed the release of pro-inflammatory mediators in LPS-induced HepG2 cells, including TNF-α, iNOS, IL-1β, IL-6, CC chemokine ligand (CCL)-2, CCL-22 and epidermal growth factor receptor (EGFR). Moreover, CXC195 inhibited the expressions and interactions of TLR4, MyD88 and TAK1, NF-κB translocation to nucleus and its DNA binding activity, phosphorylation of ERK1/2, p38 and JNK. Our results suggested that treatment with CXC195 could attenuate the TLR4-mediated proliferation and inflammatory response in LPS-induced HepG2 cells, thus might be beneficial for the treatment of HCC.

Keywords: CXC195; Hepatocellular carcinoma; Inflammation; NF-κB; Proliferation; TLR4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular / metabolism
  • Cell Cycle
  • Cell Proliferation / drug effects
  • Cell Survival
  • Gene Expression Regulation, Neoplastic*
  • Hep G2 Cells
  • Humans
  • Inflammation / metabolism
  • Lipopolysaccharides
  • Liver Neoplasms / metabolism
  • MAP Kinase Kinase Kinases / metabolism*
  • MAP Kinase Signaling System
  • Myeloid Differentiation Factor 88 / metabolism*
  • NF-kappa B / metabolism*
  • Piperazines / pharmacology*
  • Pyrazines / pharmacology*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • CXC 195
  • Lipopolysaccharides
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Piperazines
  • Pyrazines
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7