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Clinical and Translational Oncology

, Volume 9, Issue 8, pp 521–530 | Cite as

Trans-platinum(II) complexes with cyclohexylamine as expectator ligand induce necrosis in tumour cells by inhibiting DNA synthesis and RNA transcription

  • V. Cepero
  • B. García-Serrelde
  • V. Moneo
  • F. Blanco
  • A. M. González-Vadillo
  • A. Álvarez-Valdés
  • C. Navarro-Ranninger
  • A. CarneroEmail author
Research Articles

Abstract

Background

Enhanced removal of cisplatin-DNA adducts has been reported as one of main causesof cell resistance to cisplatin. This particular resistance mechanism may be circumvented by platinum complexes that bind differently to DNA. One line of work is focussed on trans platinum complexes, some of which exhibit antitumour activity similar to or even higher than that of their cis counterparts.

Methods

We synthesised new trans platinum complexes, trans-[PtCl2(cyclohexylamine) (dimethylamine)] and trans-[PtCl2(OH)2(cyclohexylamine) (dimethylamine)], previously evaluated as cytotoxic agents towards different cancer and normal cell lines. These trans platinum compounds were highly effective against a panel of tumoral cell lines either sensitive to or with acquired resistance to cisplatin.

Results

In the present work we examined the mechanisms induced by these compounds to cause tumour cells toxicity. We have found that these compounds induced a complete blockade at the S phase of the cell cycle inhibiting total mRNA transcription and precluding p53 activation.

Conclusion

In contrast to other DNA-damaging agents, these compounds do not induce senescence-associated permanent arrest. Furthermore, only a small percentage of these cells enter into apoptosis, with most of the population dying by a necrosis-like mechanism.

Key words

Antitumour drugs Platinum anticancer drugs Transplatin Cytotoxic activity Cell cycle 

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Copyright information

© Feseo 2007

Authors and Affiliations

  • V. Cepero
    • 1
  • B. García-Serrelde
    • 1
  • V. Moneo
    • 1
  • F. Blanco
    • 1
  • A. M. González-Vadillo
    • 2
  • A. Álvarez-Valdés
    • 2
  • C. Navarro-Ranninger
    • 2
  • A. Carnero
    • 1
    Email author
  1. 1.Programa de Terapias ExperimentalesCentro Nacional de Investigaciones Oncológicas (CNIO)MadridSpain
  2. 2.Departamento de Química InorgánicaUniversidad Autónoma de MadridMadridSpain

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