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Increased breast cancer cell toxicity by palladination of the polyamine analogue N-1,N-11-bis(ethyl)norspermine

Author:
  • Tania M. Silva
  • Sonia M. Fiuza
  • Maria P. M. Marques
  • Lo Persson
  • Stina Oredsson
Publishing year: 2014
Language: English
Pages: 339-352
Publication/Series: Amino Acids
Volume: 46
Issue: 2
Document type: Journal article
Publisher: Springer

Abstract english

Breast cancer is one of the most common malignant tumor forms among women and many women succumb to their disease. Thus, new anticancer agents that can efficiently improve patient survival are of the utmost importance. In this study, the effects of the polyamine analogues N (1),N (11)-bis(ethyl)norspermine (BENSpm) and N (1)-cyclo-propylmethyl-N (11)-ethylnorspermine (CPENSpm) and the synthesized dinuclear complexes Pd(2)BENSpm (Pd-BENSpm), Pt(2)CPENSpm (Pt-CPENSpm) and Pd(2)Spm (Pd-Spm) were investigated in normal-like breast epithelial MCF-10A cells and the breast cancer cell lines JIMT-1 and L56BR-C1. The overall data show that palladination of BENSpm resulted in enhanced cytotoxicity, in contrast to platination of CPENSpm that reduced cytotoxicity, which might be explained by differences in the cellular uptake of Pd-BENSpm and Pt-CPENSpm. BENSpm and Pd-BENSpm treatment reduced the CD44(+)CD24(-) putative cancer stem cell population, evaluated by flow cytometry. Furthermore, Pd-BENSpm was the most efficient compound regarding induction of DNA damage and decrease in colony formation in soft agar. Pt-CPENSpm and Pd-Spm, on the other hand, were shown to be the least toxic compounds of all tested. Pd-Spm efficiently reduced the cellular glutathione levels, which probably was a consequence of its metabolic inactivation by conjugation to this endogenous thiol. The normal-like cells were found to be less sensitive to the agents than the breast cancer cells. Our findings show that Pd-BENSpm exhibits promising anticancer effects which render it suitable for further optimization to develop a new metal-based chemotherapeutic drug for breast cancer treatment.

Keywords

  • Pharmacology and Toxicology
  • Breast cancer
  • Polyamine analogues
  • Palladium (Pd)(II) complexes
  • Platinum (Pt)(II) complexes
  • DNA damage
  • Cancer stem cells

Other

Published
  • Biogenic Amines
  • ISSN: 0939-4451
Stina Oredsson
E-mail: stina [dot] oredsson [at] biol [dot] lu [dot] se

Professor

Functional zoology

+46 46 222 94 97

B-C208

4

Principal investigator

LUCC - Lund University Cancer Centre

Research group

Animal Physiology

Projects

Cell proliferation

Doctoral students and postdocs

PhD Students, main supervisor

Wendy Soria Sotillo

PhD Students, assistant supervisor

Atena Malakpour Permlid