Artificial zinc(II) complexes regulate cell cycle and apoptosis-related genes in tumor cell lines

Jian Gao, Ya Guang Liu, Yaqing Zhou, Linda M. Boxer, F. Ross Woolley, Ralph A. Zingaro

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Various proteins involved in transcriptional regulation possess highly selective DNA-binding domains, known as zinc fingers. However, little is known about small-molecule zinc(II) complexes in the regulation of gene expression and programmed cell death. A new family of zinc(II) complexes is reported, which might be useful against human cancer cells. By using template synthesis and in vitro cell-line screening, a set of zinc(II) complexes has been found to induce apoptosis of cancer cells and display single-reagent in vitro cytotoxicity. The method used to synthesize the molecules resulted in "built-in" luminescent behavior. Confocal optical imaging clearly demonstrated penetration through the cell membrane by these metal complexes. We have discovered that C3, the meso-zinc(II) complex is an extremely efficient regulator of the cell cycle and anti-apoptosis genes bcl-2 and bcl-xL. This study provides a new insight into the development of zinc(II) complexes as potential drugs.

Original languageEnglish (US)
Pages (from-to)332-340
Number of pages9
JournalChemBioChem
Volume8
Issue number3
DOIs
StatePublished - Feb 12 2007

Keywords

  • Antitumor agents
  • Breast cancer
  • Gene expression
  • Transcription factors
  • Zinc

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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