Alpha fetoprotein antagonises benzyl isothiocyanate inhibition of the malignant behaviors of hepatocellular carcinoma cells

Oncotarget. 2016 Nov 15;7(46):75749-75762. doi: 10.18632/oncotarget.12407.

Abstract

Benzyl isothiocyanate (BITC) is a dietary isothiocyanate derived from cruciferous vegetables. Recent studies showed that BITC inhibited the growth of many cancer cells, including hepatocellular carcinoma (HCC) cells. Alpha-fetoprotein (AFP) is a important molecule for promoting progression of HCC, in the present investigation, we explore the influence of AFP on the role of BITC in the malignant behaviours of HCC cells, and the potential underlying mechanisms. We found thatBITC inhibited viability, migration, invasion and induced apoptosis of human liver cancer cell lines, Bel 7402(AFP producer) and HLE(non-AFP producer) cells in vitro. The role of BITC involve in promoting actived-caspase-3 and PARP-1 expression, and enhancing caspase-3 activity but decreasing MMP-2/9, survivin and CXCR4 expression. AFP antagonized the effect of BITC. This study suggests that BITC induced significant reductions in the viability of HCC cell lines. BITC may activate caspase-3 signal and inhibit the expression of growth- and metastasis-related proteins; AFP is an pivotal molecule for the HCC chemo-resistance of BITC.

Keywords: apoptosis; benzyl isothiocyanate (BITC); hepatocellular carcinoma; alpha-fetoprotein.

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Isothiocyanates / pharmacology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Poly (ADP-Ribose) Polymerase-1 / genetics
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • alpha-Fetoproteins / metabolism*
  • alpha-Fetoproteins / pharmacology

Substances

  • Isothiocyanates
  • Receptors, CXCR4
  • alpha-Fetoproteins
  • benzyl isothiocyanate
  • Poly (ADP-Ribose) Polymerase-1
  • Caspase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9