Anti-cancer effects of a novel compound HS-113 on cell growth, apoptosis, and angiogenesis in human hepatocellular carcinoma cells

Cancer Lett. 2011 Jul 28;306(2):190-6. doi: 10.1016/j.canlet.2011.03.005. Epub 2011 Apr 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-113 was synthesized as a novel compound, N-(5-(2-bromobenzyl) thiazole-2-yl) benzofuran-2-carboxamide and its cytotoxic activity and anti-cancer effect were examined in human HCC cells. HS-113 strongly suppressed growth of HCC cells in a dose-dependent manner, induced apoptosis by increasing the proportion of sub-G1 apoptotic cells, and caused cell cycle arrest at G0/G1 phase. Also, HS-113 increased the expression of p27 and decreased that of cyclin D1 associated with cell cycle arrest. Apoptosis by HS-113 was confirmed by DAPI and TUNEL staining, and the increases of the cleaved PARP and caspase-3 were observed. Furthermore, HS-113 decreased protein expression of HIF-1α and secretion of VEGF, and inhibited the tube formation of HUVECs. These results showed that HS-113 not only inhibited cell growth and angiogenesis, but also induced apoptosis of human HCC cells. We suggest that HS-113 may be a potential candidate for cancer therapy against HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Benzofurans / chemical synthesis
  • Benzofurans / pharmacology*
  • Blotting, Western
  • Carcinoma, Hepatocellular / blood supply*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Neovascularization, Pathologic / prevention & control*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Thiazoles / chemical synthesis
  • Thiazoles / pharmacology*
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Umbilical Veins / metabolism

Substances

  • Antineoplastic Agents
  • Benzofurans
  • Cell Cycle Proteins
  • N-(5-(2-bromobenzyl)thiazole-2-yl)benzofuran-2-carboxamide
  • Proto-Oncogene Proteins c-bcl-2
  • Thiazoles
  • Poly(ADP-ribose) Polymerases