title: The Anticancer Activity of Organotelluranes: Potential Role in Integrin Inactivation.
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.
authors.affiliation: The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel.|C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.|Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, 7610001, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Silberman
authors.affiliation: C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Yona
authors.initials: Y
authors.lastname: Kalechman
authors.affiliation: The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Hirsch
authors.affiliation: C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Erlich
authors.affiliation: C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel. benjamin.sredni@biu.ac.il.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sredni
authors.affiliation: The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel. amnon.albeck@biu.ac.il.
authors.forename: Amnon
authors.initials: A
authors.lastname: Albeck
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D013691:Tellurium / Q000737:chemistry*; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D039041:Integrin alpha4beta1; D016023:Integrins; D009942:Organometallic Compounds; D013691:Tellurium
keywords: VLA-4; cancer; inhibitors; integrins; labile ligands; organotelluranes