The organotelluride catalyst LAB027 prevents colon cancer growth in the mice
| Autor: | Romain Coriat, Mahaut Leconte, Bernard Weill, A Vienne, Wioleta Marut, Carole Nicco, Claus Jacob, L B Ba, Frédéric Batteux, Mandy Doering, Jérôme Alexandre, Christiane Chéreau |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Programmed cell death mice Organoplatinum Compounds Colorectal cancer Immunology Transplantation Heterologous Antineoplastic Agents Apoptosis Biology Catalysis 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine In vivo tellurium Cell Line Tumor medicine Organometallic Compounds Cytotoxic T cell Animals Humans 030304 developmental biology Cell Proliferation reactive oxygen species 0303 health sciences Cell growth oxaliplatin Cell Biology Hydrogen Peroxide medicine.disease Glutathione digestive system diseases 3. Good health Oxaliplatin Disease Models Animal Oxidative Stress Biochemistry colon cancer Cell culture 030220 oncology & carcinogenesis Caspases Colonic Neoplasms Cancer research Original Article Oxidation-Reduction medicine.drug Naphthoquinones |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|