Casiopeina III-ia induces apoptosis in HCT-15 cells in vitro through caspase-dependent mechanisms and has antitumor effect in vivo

Biometals. 2008 Feb;21(1):17-28. doi: 10.1007/s10534-007-9089-4. Epub 2007 Mar 28.

Abstract

The aim of this study was to evaluate the in vitro and in vivo effects of the new chemotherapy agent Casiopeina III-ia [(4,4'-dimethyl-2,2'-bipiridine)(acetylacetonate) Copper (II) nitrate] on HCT-15 (p53-/-) colon cellular line. In vitro, the drug reduced the viability and induced necrosis and apoptosis in a dose dependent manner, without affecting cell cycle phases. Apoptosis was related to Bax increasing levels, suggesting a caspase-dependent mechanism of death, as verified by nucleosomal fragmentation of DNA. In vivo, the antitumor activity of Casiopeina III-ia was tested in HCT-15 cells transplanted to nude mice. In this study we will show that the novel antineoplastic agent Casiopeina III-ia is active on this colon tumor line, setting out as a good candidate for the treatment of colon tumors refractory to chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Body Weight / drug effects
  • Caspases / metabolism*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Xenograft Model Antitumor Assays*
  • bcl-2-Associated X Protein / metabolism

Substances

  • (4,4-dimethyl-2,2-bipyridine)(acetylacetonate)copper(II)
  • Organometallic Compounds
  • bcl-2-Associated X Protein
  • Caspases