Moon Ji-Hong, Jeong Jae-Kyo, Park Sang-Youel
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
Oncol Rep. 2015 Mar;33(3):1171-6. doi: 10.3892/or.2014.3676. Epub 2014 Dec 18.
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.
去铁胺（DFO）是一种铁螯合剂，对于铁过载患者在改善生活质量和总体生存率方面有众多临床应用。此外，实验性铁螯合剂已显示出强大的抗癌特性。本研究调查了DFO对结肠癌细胞中肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导的凋亡的影响及其相关机制。实验结果表明，DFO处理通过增加人结肠癌细胞中Akt激活和降低半胱天冬酶激活来抑制TRAIL介导的癌细胞凋亡。此外，DFO处理诱导自噬通量，而自噬抑制剂氯喹可阻断DFO介导的对TRAIL诱导凋亡的抑制作用。本研究表明，DFO通过自噬途径抑制TRAIL介导的肿瘤细胞死亡，结果提示强效抗癌剂DFO可以成为包括TRAIL蛋白在内的抗肿瘤治疗的抑制剂。
