Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.
Cancer Lett. 2010 Jan 28;287(2):224-30. doi: 10.1016/j.canlet.2009.06.013. Epub 2009 Jul 24.
In this study, we demonstrate for the first time that cystamine, an inhibitor of transglutaminase 2 (TG2), enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in Caki cells, but not in normal human mesangial cells. Cystamine plus TRAIL-induced down-regulation of c-FLIP was recovered to basal levels by addition of the pancaspase inhibitor, z-VAD. The forced expression of c-FLIP attenuated cystamine plus TRAIL-mediated apoptosis in Caki cells. Although, cells expressing high levels of TG2 were more sensitive to cystamine plus TRAIL-mediated apoptosis than were cells expressing low levels of TG2, cystamine plus TRAIL-mediated apoptosis in the cell line expressing high levels of TG2 was reduced when TG2 levels were knocked down with siRNA. These results indicate that the level of TG2 modulates cystamine plus TRAIL-induced apoptosis. Taken together, the present findings suggest that cystamine may be an effective sensitizer of TRAIL-induced apoptosis in cancer cells expressing high levels of TG2.
在这项研究中，我们首次证明，半胱胺作为转谷氨酰胺酶 2（TG2）的抑制剂，可增强 Caki 细胞而非正常人肾小球系膜细胞中肿瘤坏死因子相关凋亡诱导配体（TRAIL）介导的细胞凋亡。半胱胺联合 TRAIL 诱导的 c-FLIP 下调可通过添加泛半胱氨酸蛋白酶抑制剂 z-VAD 恢复至基础水平。强制表达 c-FLIP 可减弱 Caki 细胞中半胱胺联合 TRAIL 诱导的细胞凋亡。尽管表达高水平 TG2 的细胞比表达低水平 TG2 的细胞对半胱胺联合 TRAIL 介导的细胞凋亡更为敏感，但当用 siRNA 敲低 TG2 水平时，高表达 TG2 的细胞系中半胱胺联合 TRAIL 介导的细胞凋亡减少。这些结果表明 TG2 水平调节半胱胺联合 TRAIL 诱导的细胞凋亡。综上所述，这些发现表明，半胱胺可能是表达高水平 TG2 的癌细胞中 TRAIL 诱导的细胞凋亡的有效敏化剂。
