Transferrin ensures survival of ovarian carcinoma cells when apoptosis is induced by TNFalpha, FasL, TRAIL, or Myc.
Transferrin ensures survival of ovarian carcinoma cells when apoptosis is induced by TNFalpha, FasL, TRAIL, or Myc.
复制标题
当 TNFα、FasL、TRAIL 或 Myc 诱导细胞凋亡时，转铁蛋白可确保卵巢癌细胞的存活。
作者：
S. Fassl;C. Leisser;S. Huettenbrenner;S. Maier;G. Rosenberger;S. Strasser;M. Grusch;G. Fuhrmann;K. Leuhuber;D. Polgar;J. Stani;B. Tichy;C. Nowotny;G. Krupitza
Myc的激活诱导人卵巢腺癌N.1细胞在血清因子限制下的凋亡然而，由Myc触发的下游机制是未知的。Myc激活和用促凋亡配体TNF α、FasL和TRAIL治疗诱导了血清剥夺条件下的H-铁蛋白表达。H-铁蛋白通过去铁胺诱导的N.1细胞凋亡螯合细胞内铁和细胞内铁螯合。补充全转铁蛋白的无血清培养基阻断了由Myc激活或用TNF α、FasL和TRAIL处理诱导的N.1细胞凋亡，而脱铁转铁蛋白并不能阻止细胞凋亡。这表明细胞内铁耗竭是细胞凋亡的触发器，并且转铁蛋白结合的铁拯救了N.1细胞。此外，原代人卵巢癌细胞的凋亡，这是由TNF α，FasL，和TRAIL诱导，也被全转铁蛋白抑制。这些数据表明，Myc激活，FasL，TNF α和TRAIL扰乱细胞铁稳态，从而引发卵巢癌细胞的凋亡，转铁蛋白铁通过重新建立这种稳态来确保生存。
The activation of Myc induces apoptosis of human ovarian adenocarcinoma N.1 cells when serum factors are limited. However, the downstream mechanism that is triggered by Myc is unknown. Myc-activation and treatment with the proapoptotic ligands TNFalpha, FasL, and TRAIL induced H-ferritin expression under serum-deprived conditions. H-ferritin chelates intracellular iron and also intracellular iron sequestration by deferoxamine-induced apoptosis of N.1 cells. Supplementation of serum-free medium with holo-transferrin blocked apoptosis of N.1 cells that was induced by Myc-activation or by treatment with TNFalpha, FasL, and TRAIL, whereas apotransferrin did not prevent apoptosis. This suggests that intracellular iron depletion was a trigger for apoptosis and that transferrin-bound iron rescued N.1 cells. Furthermore, apoptosis of primary human ovarian carcinoma cells, which was induced by TNFalpha, FasL, and TRAIL, was also inhibited by holo-transferrin. The data suggest that Myc-activation, FasL, TNFalpha, and TRAIL disturbed cellular iron homeostasis, which triggered apoptosis of ovarian carcinoma cells and that transferrin iron ensured survival by re-establishing this homeostasis.