Formamidinodoxorubicins are more potent than doxorubicin as apoptosis inducers in human breast cancer cells

Anticancer Res. 2015 Apr;35(4):1935-40.

Abstract

Background/aim: The ability of five formamidinodoxorubicins to induce apoptosis of MCF-7 breast cancer cells was tested. All these compounds were modified at C-3' and contain a formamidine group (-N=CH-NRR), with the rest of the cyclic secondary amine (HNRR) of a gradually increasing ring size.

Materials and methods: Cytotoxicity was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To analyze apoptosis, double staining using fluorescence probes Hoechst 33258/propidium iodide (PI) and annexin V- Fluorescein isothiocyanate/PI was carried-out. Additionally, the TdT-mediated dUTP nick-end labelling test and activity of caspase 3 were determined.

Results: The four tested derivatives displayed a significant increase in antiproliferative activity in comparison to doxorubicin. All of the tested derivatives induced caspase-dependent apoptosis of MCF-7 cells.

Conclusion: DOX-F MOR and DOX-F PAZ analogs are more potent apoptosis inducers than doxorubicin.

Keywords: Apoptosis; cytotoxicity; formamidine anthracyclines; necrosis.

MeSH terms

  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / analogs & derivatives
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • MCF-7 Cells
  • Membrane Potential, Mitochondrial / drug effects

Substances

  • Annexin A5
  • Doxorubicin
  • Caspase 3