The Anticancer Activity of Organotelluranes: Potential Role in Integrin Inactivation

Chembiochem. 2016 May 17;17(10):918-27. doi: 10.1002/cbic.201500614. Epub 2016 Apr 25.

Abstract

Organic Te(IV) compounds (organotelluranes) differing in their labile ligands exhibited anti-integrin activities in vitro and anti-metastatic properties in vivo. They underwent ligand substitution with l-cysteine, as a thiol model compound. Unlike inorganic Te(IV) compounds, the organotelluranes did not form a stable complex with cysteine, but rather immediately oxidized it. The organotelluranes inhibited integrin functions, such as adhesion, migration, and metalloproteinase secretion mediation in B16F10 murine melanoma cells. In comparison, a reduced derivative with no labile ligand inhibited adhesion of B16F10 cells to a significantly lower extent, thus pointing to the importance of the labile ligands of the Te(IV) atom. One of the organotelluranes inhibited circulating cancer cells in vivo, possibly by integrin inhibition. Our results extend the current knowledge on the reactivity and mechanism of organotelluranes with different labile ligands and highlight their clinical potential.

Keywords: VLA-4; cancer; inhibitors; integrins; labile ligands; organotelluranes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Disease Models, Animal
  • Integrin alpha4beta1 / antagonists & inhibitors
  • Integrin alpha4beta1 / metabolism
  • Integrins / antagonists & inhibitors
  • Integrins / metabolism*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology*
  • Organometallic Compounds / therapeutic use
  • Protein Binding / drug effects
  • Tellurium / chemistry*
  • Transplantation, Homologous

Substances

  • Antineoplastic Agents
  • Integrin alpha4beta1
  • Integrins
  • Organometallic Compounds
  • Tellurium