New extracellular resistance mechanism for cisplatin

Corey R. Centerwall, Deborah J. Kerwood, Jerry Goodisman, Bonnie B. Toms, James C. Dabrowiak

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The HSQC NMR spectrum of 15N-cisplatin in cell growth media shows resonances corresponding to the monocarbonato complex, cis-[Pt(NH3)2(CO3)Cl]-, 4, and the dicarbonato complex, cis-[Pt(NH3)2(CO3)2]-2, 5, in addition to cisplatin itself, cis-[Pt(NH3)2Cl2], 1. The presence of Jurkat cells reduces the amount of detectable carbonato species by (2.8 ± 0.7) fmol per cell and has little effect on species 1. Jurkat cells made resistant to cisplatin reduce the amount of detectable carbonato species by (7.9 ± 5.6) fmol per cell and also reduce the amount of 1 by (3.4 ± 0.9) fmol per cell. The amount of detectable carbonato species is also reduced by addition of the drug to medium that has previously been in contact with normal Jurkat cells (cells removed); the reduction is greater when drug is added to medium previously in contact with resistant Jurkat cells (cells removed). This shows that the platinum species are modified by a cell-produced substance that is released to the medium. Since the modified species have been shown not to enter or bind to cells, and since resistant cells modify more than non-resistant cells, the modification constitutes a new extracellular mechanism for cisplatin resistance which merits further attention.

Original languageEnglish (US)
Pages (from-to)1044-1049
Number of pages6
JournalJournal of Inorganic Biochemistry
Volume102
Issue number5-6
DOIs
StatePublished - May 2008

Keywords

  • Cisplatin
  • Extracellular
  • HSQC NMR
  • Resistance

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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  • Cite this

    Centerwall, C. R., Kerwood, D. J., Goodisman, J., Toms, B. B., & Dabrowiak, J. C. (2008). New extracellular resistance mechanism for cisplatin. Journal of Inorganic Biochemistry, 102(5-6), 1044-1049. https://doi.org/10.1016/j.jinorgbio.2008.01.008