Anticancer effects of KI-10F: a novel compound affecting apoptosis, angiogenesis and cell growth in colon cancer

Int J Oncol. 2012 Nov;41(5):1715-22. doi: 10.3892/ijo.2012.1609. Epub 2012 Aug 27.

Abstract

The anticancer effect of a new pyrazole derivative, KI-10F (2-(4-(2-(4-(dimethylamino) phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol‑1-yl) acetonitrile)•3.5HCl) was evaluated in human colon cancer cells. KI-10F strongly suppressed the growth of human colon cancer cells and induced apoptosis by increasing the proportion of sub-G1 presenting apoptotic cells as well as causing cell cycle arrest at the G2/M phase. Apoptosis by KI-10F was confirmed by observation of an increase in the expression of cleaved caspase-3, caspase-8, caspase-9 and Bax, and the decrease of Bcl-2. Decreased expression of HIF-1α and VEGF, and the inhibition of HUVEC tube formation and migration showed that KI-10F effectively inhibited the angiogenesis process. Furthermore, in vivo study in a mouse xenograft model showed that KI-10F produced a stronger antitumor activity than 5-FU, a conventional anticancer drug prescribed for the treatment of colon cancer. The effects of KI-10F on tumor proliferation (PCNA), angiogenesis (CD34) and apoptosis (cleaved caspase-3) were evaluated by immunohistochemistry using isolated tumor tissue samples. Taken together, our results demonstrated that KI-10F induces apoptosis and inhibits cell growth and angiogenesis both in vitro and in vivo. We suggest that KI-10F is an effective chemotherapeutic candidate for use against colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetonitriles / administration & dosage
  • Acetonitriles / chemistry
  • Acetonitriles / pharmacology*
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • HT29 Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic* / drug therapy
  • Pyrazoles / administration & dosage
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • 2-(4-(2-(4-(dimethylamino)phenyl)pyridin-4-yl)-5-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetonitrile
  • Acetonitriles
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Pyrazoles