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

Jian Gao, Ya-guang Liu, Renbin Liu, Ralph A. Zingaro

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Fingerprint

Platinum
Cells
Neoplasms
Platinum compounds
Annexin A5
Fibroblasts
Cytotoxicity
Platinum Compounds
Assays
Genes
Regulator Genes
Apoptosis
Ligands
Trastuzumab
Breast Neoplasms
Cell Line
Growth

Keywords

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

ASJC Scopus subject areas

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

Cite this

Herceptin-platinum(II) binding complexes : Novel cancer-cell-specific agents. / Gao, Jian; Liu, Ya-guang; Liu, Renbin; Zingaro, Ralph A.

In: ChemMedChem, Vol. 3, No. 6, 16.06.2008, p. 954-962.

Research output: Contribution to journalArticle

Gao, Jian ; Liu, Ya-guang ; Liu, Renbin ; Zingaro, Ralph A. / Herceptin-platinum(II) binding complexes : Novel cancer-cell-specific agents. In: ChemMedChem. 2008 ; Vol. 3, No. 6. pp. 954-962.
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