Herceptin-platinum(II) binding complexes: Novel cancer-cell-specific agents

Jian Gao, Ya Guang Liu, Renbin Liu, Ralph A. Zingaro

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

We report a new series of Herceptin-platinum(II) binding complexes, Her-nLPtII (Her denotes Herceptin; L denotes diamino ligands and L=L1-L4; n=1, 5, or 10). Solution chemistry studies have shown that these complexes are stable under physiological conditions (pH 7.4in PBS). The platinum(II) compound L1PtIICl2 inhibits the growth of a panel of human cancer cell lines at submicromolar concentrations. Remarkable cancer-cell-specific cytotoxicity was observed with Her-nL1PtII (n=1, 5, 10) toward Her2/neu-overexpressing cancer cells (SK-BR-3 and SK-OV-3) over normal fibroblast cells. Annexin V apoptosis assays in SK-BR-3 and low-Her2/neu-expressing MCF-7 breast cancer cells further confirmed the critical role of Herceptin with this cancer-cell-specific agent. It was also found that the L1PtIICl2 complex is an efficient regulator of the apoptotic genes Bcl-2 in the treated SK-BR-3 cells. Also, enhanced regulatory effects were observed in Her-10L1PtII. Taken together, this study suggests a new approach for the development of mAb-platinum(II)-based targeting agents for the treatment of human cancers.

Original languageEnglish (US)
Pages (from-to)954-962
Number of pages9
JournalChemMedChem
Volume3
Issue number6
DOIs
StatePublished - Jun 16 2008

Keywords

  • Antibodies
  • Apoptosis
  • Cancer
  • Her2/neu
  • Platinum(II) compounds
  • mRNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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