Cytotoxic activities, cellular uptake, gene regulation, and optical imaging of novel platinum(II) complexes

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A new class of platinum(II) coordination complexes and their dye tagged conjugates has been synthesized from N-substituted diaminocyclohexane ligands. The in vitro anticancer activities of the platinum compounds have been validated against the breast cancer cell-line MCF-7 and the normal cell-line MCF-10A via sulforhodamine B and colony formation assay. The platinum compounds and the corresponding metal-free ligands exhibited higher drug efficiencies than cisplatin and oxaliplatin against MCF-7 cells. Cellular uptake and DNA-bound Pt were demonstrated by atomic absorption spectroscopy. The platinum complexes displayed increased cellular accumulation and DNA binding as compared with cisplatin. Real-time reverse transcription polymerase chain reaction assay was employed to investigate drug effects on mRNA expression in MCF-7 cells. The results indicated that the study compounds are effective in regulating cyclin D1, Bcl-2, and p53 genes; yet, oxaliplatin is less effective in manipulating those genes. The luminescent probe that was integrated into the platinum complexes made it possible to monitor cellular drug distribution using optical imaging. Targeting of tumor cell nuclei by the study compounds was confirmed by confocal microscopy. Taken together, these new platinum(II)-based antitumor agents are different from marketed platinum drugs in several critical aspects and could have potential in cancer therapy.

Original languageEnglish (US)
Pages (from-to)1705-1712
Number of pages8
JournalChemical Research in Toxicology
Volume22
Issue number10
DOIs
StatePublished - Oct 19 2009

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Optical Imaging
Platinum
oxaliplatin
Gene expression
MCF-7 Cells
Imaging techniques
Platinum Compounds
Genes
lissamine rhodamine B
Pharmaceutical Preparations
Cisplatin
Assays
Cells
Ligands
bcl-2 Genes
Cell Line
Atomic spectroscopy
Confocal microscopy
Polymerase chain reaction
DNA

ASJC Scopus subject areas

  • Toxicology

Cite this

Cytotoxic activities, cellular uptake, gene regulation, and optical imaging of novel platinum(II) complexes. / Gao, Jian; Liu, Ya-guang; Zingaro, Ralph A.

In: Chemical Research in Toxicology, Vol. 22, No. 10, 19.10.2009, p. 1705-1712.

Research output: Contribution to journalArticle

Gao, Jian ; Liu, Ya-guang ; Zingaro, Ralph A. / Cytotoxic activities, cellular uptake, gene regulation, and optical imaging of novel platinum(II) complexes. In: Chemical Research in Toxicology. 2009 ; Vol. 22, No. 10. pp. 1705-1712.
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