title: The organotelluride catalyst LAB027 prevents colon cancer growth in the mice.
abstract: Organotellurides are newly described redox-catalyst molecules with original pro-oxidative properties. We have investigated the in vitro and in vivo antitumoral effects of the organotelluride catalyst LAB027 in a mouse model of colon cancer and determined its profile of toxicity in vivo. LAB027 induced an overproduction of H(2)O(2) by both human HT29 and murine CT26 colon cancer cell lines in vitro. This oxidative stress was associated with a decrease in proliferation and survival rates of the two cell lines. LAB027 triggered a caspase-independent, ROS-mediated cell death by necrosis associated with mitochondrial damages and autophagy. LAB027 also synergized with the cytotoxic drug oxaliplatin to augment its cytostatic and cytotoxic effects on colon cancer cell lines but not on normal fibroblasts. The opposite effects of LAB027 on tumor and on non-transformed cells were linked to differences in the modulation of reduced glutathione metabolism between the two types of cells. In mice grafted with CT26 tumor cells, LAB027 alone decreased tumor growth compared with untreated mice, and synergized with oxaliplatin to further decrease tumor development compared with mice treated with oxaliplatin alone. LAB027 an organotelluride catalyst compound synergized with oxaliplatin to prevent both in vitro and in vivo colon cancer cell proliferation while decreasing the in vivo toxicity of oxaliplatin. No in vivo adverse effect of LAB027 was observed in this model.
authors.affiliation: Université Paris Descartes, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP), Laboratoire d'immunologie, France.
authors.forename: R
authors.initials: R
authors.lastname: Coriat
authors.forename: W
authors.initials: W
authors.lastname: Marut
authors.forename: M
authors.initials: M
authors.lastname: Leconte
authors.forename: L B
authors.initials: LB
authors.lastname: Ba
authors.forename: A
authors.initials: A
authors.lastname: Vienne
authors.forename: C
authors.initials: C
authors.lastname: Chéreau
authors.forename: J
authors.initials: J
authors.lastname: Alexandre
authors.forename: B
authors.initials: B
authors.lastname: Weill
authors.forename: M
authors.initials: M
authors.lastname: Doering
authors.forename: C
authors.initials: C
authors.lastname: Jacob
authors.forename: C
authors.initials: C
authors.lastname: Nicco
authors.forename: F
authors.initials: F
authors.lastname: Batteux
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D009285:Naphthoquinones / Q000627:therapeutic use* / Q000633:toxicity; D009942:Organometallic Compounds / Q000627:therapeutic use* / Q000633:toxicity; D009944:Organoplatinum Compounds / Q000633:toxicity; D000077150:Oxaliplatin; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013691:Tellurium / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C568136:LAB 027; D009285:Naphthoquinones; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D006861:Hydrogen Peroxide; D020169:Caspases; D005978:Glutathione; D013691:Tellurium