Luzi Carla, Brisdelli Fabrizia, Iorio Roberto, Bozzi Argante, Carnicelli Veronica, Di Giulio Antonio, Lizzi Anna Rita
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Cell Biochem Funct. 2017 Jan;35(1):33-41. doi: 10.1002/cbf.3242. Epub 2017 Jan 3.
Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12.5 μM). Western blot analysis showed that key apoptotic regulators including Bax, Bcl-2, Sirt1, Mcl-1, and PARP-1 were modulated by 1.25 μM of apo-bLf. In the same cell line, apo-bLf induced apoptosis together with poly (ADP-ribose) polymerase cleavage, caspase activation, and a significant drop of NAD . In addition, apo-bLf-treated HeLa cells showed a marked increase of reactive oxygen species level and a significant GSH depletion. On the whole, apo-bLf triggered apoptosis of HeLa cells upon oxygen radicals burst and GSH decrease.
乳铁蛋白（Lf）是一种存在于人体分泌物中的80 kDa阳离子铁结合糖蛋白，是一种具有显著抗菌活性的化合物。在本研究中，研究了无铁牛乳铁蛋白（脱铁乳铁蛋白）对人上皮癌细胞（HeLa）的凋亡作用，并分析了其与活性氧和谷胱甘肽（GSH）水平的关系。无铁牛乳铁蛋白的凋亡作用在处理48小时后抑制了HeLa细胞的生长，而在测试浓度范围（1至12.5 μM）内，双铁乳铁蛋白无效。蛋白质免疫印迹分析表明，包括Bax、Bcl-2、Sirt1、Mcl-1和PARP-1在内的关键凋亡调节因子受到1.25 μM脱铁乳铁蛋白的调节。在同一细胞系中，脱铁乳铁蛋白诱导凋亡，同时伴有聚（ADP-核糖）聚合酶裂解、半胱天冬酶激活和NAD显著下降。此外，经脱铁乳铁蛋白处理的HeLa细胞显示活性氧水平显著升高，谷胱甘肽显著消耗。总体而言，脱铁乳铁蛋白在氧自由基爆发和谷胱甘肽减少时触发HeLa细胞凋亡。
