Biologic activity of a dinuclear Pd(II)-spermine complex toward human breast cancer

Sónia M. Fiuza, Jon Holy, Luis A.E. Batista de Carvalho, Maria P.M. Marques

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

A dinuclear palladium-based complex (Pd2-Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF-7 and MDA-MB-231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd2-Spm is more effective against the estrogen receptors [ER(-)] cell line MDA-MB-231, while cDDP displayed better results for the ER(+) MCF-7 cell line. It was shown that, like cDDP, Pd2-Spm triggers phosphorylation of H2AX, indicating that this compound damages DNA. Apart from DNA, Pd2-Spm also targets the cytoskeleton having a greater impact on cell morphology than cDDP. Pd2-Spm and cDDP have opposite antiproliferative activities in the presence of the PI3K inhibitor wortmannin. Furthermore, Pd2-Spm at an optimized concentration displays a rapid antiproliferative effect as opposed to cDDP, which seems to have a slower kinetics. The results point to a distinct mechanism of action for each of these complexes, which may explain their synergistic action when coadministrated. A spermine dinuclear palladium(II) complex (Pd2-Spm) was synthesized and tested towards two human breast cancer cell lines (MCF-7 and MDA-MB-231) as to its antiproliferative properties, and compared to the widely used drug cisplatin (cDDP). For optimized concentrations Pd2-Spm induced a rapid growth-inhibiting effect, as opposed to cDDP which seems to have a slower kinetics. The results evidence a possible distinct mechanism of action for these two Pt(II) complexes, which may explain their synergistic activity when co-administered.

Original languageEnglish (US)
Pages (from-to)477-488
Number of pages12
JournalChemical Biology and Drug Design
Volume77
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • Gamma-H2AX
  • Human breast cancer
  • Pd(II) complex
  • Polynuclear
  • Spermine
  • Wortmannin

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