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Polypyridyl Zinc(II)-Indomethacin Complexes with Potent Anti-Breast Cancer Stem Cell Activity

Tiffany K Rundstadler1, Arvin Eskandari2, Sarah M Norman3

  • 1Department of Chemistry, King's College London, London SE1 1DB, UK. tiffany.rundstadler@etu.unistra.fr.

Molecules (Basel, Switzerland)
|September 6, 2018
PubMed

Insights

New zinc(II) complexes show potent anti-cancer activity. These compounds effectively target both cancer stem cells (CSCs) and bulk tumor cells, offering a promising strategy for complete tumor elimination.

Area of Science:

  • Medicinal Chemistry
  • Cancer Biology
  • Nanotechnology

Background:

  • Cancer stem cells (CSCs) drive tumor relapse and metastasis.
  • Current anti-CSC therapies often focus on biologics or organic molecules.
  • Previous research highlighted copper(II) complexes for selective CSC targeting.

Purpose of the Study:

  • To investigate the anti-cancer efficacy of novel redox-inactive zinc(II) complexes.
  • To evaluate the potential of these zinc(II) compounds against breast CSCs and bulk cancer cells.
  • To compare the activity of zinc(II) complexes with established CSC-targeting agents like salinomycin.

Main Methods:

  • Synthesis and characterization of zinc(II)-phenanthroline-indomethacin complexes.
  • In vitro assessment of cytotoxicity against breast CSCs and bulk breast cancer cells.
  • Evaluation of mammosphere formation and viability assays.

Main Results:

  • Zinc(II) complexes demonstrated potent cytotoxicity against both breast CSCs and bulk cancer cells.
  • The compounds exhibited efficacy in the submicromolar to micromolar range.
  • Some zinc(II) complexes matched or surpassed salinomycin in reducing mammosphere growth and viability.

Conclusions:

  • Redox-inactive zinc(II) complexes are effective against breast CSCs and bulk tumor cells.
  • These zinc(II) compounds represent a novel therapeutic strategy for eliminating entire tumor populations.
  • This study is the first to report on the anti-breast CSC activity of zinc(II)-containing compounds.
Keywords:
bioinorganic chemistrymetallopharmaceuticalsnonsteroidal anti-inflammatory drugzinc

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