The effect of HS-111, a novel thiazolamine derivative, on apoptosis and angiogenesis of hepatocellular carcinoma cells

Arch Pharm Res. 2012 Mar;35(4):747-54. doi: 10.1007/s12272-012-0420-4. Epub 2012 May 3.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies, yet there have been no significant advances in effective therapeutics. In this study, HS-111 was synthesized as a novel thiazolamine derivative, N-(5-(2-chlorobenzyl) thiazole-2-yl) benzofuran-2-carboxamide, and its anticancer effect and mechanism were examined in human HCC cells. HS-111 strongly suppressed the growth of HCC cells in a dose-dependent manner. Also, apoptosis by HS-111 was identified by DAPI and TUNEL staining, and the increases of the cleaved caspase-3 were observed. In addition, HS-111 decreased protein expression of hypoxia-inducible factor (HIF-1α) and secretion of vascular endothelial growth factor (VEGF), and inhibited tube formation and the migration of human umbilical vein endothelial cells (HUVECs). These results showed that HS-111 not only inhibited cell growth and angiogenesis, but also induced apoptosis of human HCC cells. We suggest that HS-111 may be a potential candidate for chemotherapy against HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Apoptosis / drug effects*
  • Benzofurans / chemistry
  • Benzofurans / pharmacology*
  • Benzofurans / therapeutic use
  • Blotting, Western
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • In Situ Nick-End Labeling
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology*
  • Molecular Structure
  • Neovascularization, Pathologic / prevention & control*
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use
  • Wound Healing / drug effects

Substances

  • Angiogenesis Inhibitors
  • Benzofurans
  • N-(5-(2-chlorobenzyl)thiazole-2-yl)benzofuran-2-carboxamide
  • Thiazoles