Artificial zinc(II) complexes regulate cell cycle and apoptosis-related genes in tumor cell lines.
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.
Gao
Jian
J
Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255, USA. gaojiantamu@yahoo.com
Liu
Ya-Guang
YG
Zhou
Yaqing
Y
Boxer
Linda M
LM
Woolley
F Ross
FR
Zingaro
Ralph A
RA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018816:Genes, cdc / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000737:chemistry*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D009942:Organometallic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D015032:Zinc