title: Deferoxamine inhibits TRAIL-mediated apoptosis via regulation of autophagy in human colon cancer cells.
abstract: Deferoxamine (DFO), an iron chelator, has numerous clinical applications for patients presenting with iron overload in regards to the improvement in the quality of life and overall survival. In addition, experimental iron chelators have demonstrated potent anticancer properties. The present study investigated the effects of DFO on TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in colon cancer cells and and the mechanism involved. The experimental results showed that DFO treatment inhibited TRAIL-mediated cancer cell apoptosis by increasing Akt activation and decreasing caspase activation in human colon cancer cells. Furthermore, DFO treatment induced autophagy flux, and chloroquine, an autophagy inhibitor, blocked DFO-mediated inhibition of TRAIL-induced apoptosis. The present study demonstrated that DFO inhibited TRAIL-mediated tumor cell death via the autophagy pathway, and the results suggest that potent anticancer agent, DFO, can be an inhibitor against antitumor therapy including TRAIL protein.
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Jae-Kyo
authors.initials: JK
authors.lastname: Jeong
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D003676:Deferoxamine / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D003676:Deferoxamine