Habel Marie-Eve, Jung Daniel
Héma-Québec, Recherche et Développement, 1009, Département de Biochimie et Microbiologie, Université Laval, route du Vallon, Sainte-Foy, Qué., Canada G1V 5C3.
Free Radic Res. 2006 Aug;40(8):789-97. doi: 10.1080/10715760500484344.
The addition of ferric citrate to Burkitt's lymphoma (BL) cell lines inhibits growth, leads to the accumulation of cells in the phase G(2)/M of the cell cycle and to the modulation of translocated c-myc expression. The increase in the labile iron pool (LIP) of iron-treated BL cells leads to cytotoxicity. Indeed, intracellular free iron catalyzes the formation of highly reactive compounds such as hydroxyl radicals and nitric oxide (NO) that damages macromolecular components of cells, eventually resulting in apoptosis. In this report, we have investigated the possible involvement of free radicals in the response of Ramos cells to iron. When added to Ramos cells, iron increased the intracellular levels of peroxide/peroxynitrite and NO. Moreover, the addition of free radicals scavengers (TROLOX and Carboxy-PTIO) neutralized the effects of iron on Ramos cells while addition of an NO donor or hydrogen peroxide (H2O2) to cells generated effects which partially mimicked those induced by iron addition. Collectively, our results suggest the involvement of free radicals as effectors in the iron specific growth inhibition of BL cells observed in vitro.
向伯基特淋巴瘤(BL)细胞系中添加柠檬酸铁可抑制其生长,导致细胞在细胞周期的G(2)/M期积累,并调节易位c-myc的表达。铁处理的BL细胞中不稳定铁池(LIP)的增加会导致细胞毒性。实际上,细胞内游离铁催化形成高反应性化合物,如羟基自由基和一氧化氮(NO),这些化合物会损害细胞的大分子成分,最终导致细胞凋亡。在本报告中,我们研究了自由基在拉莫斯细胞对铁的反应中可能的作用。当添加到拉莫斯细胞中时,铁会增加细胞内过氧化物/过氧亚硝酸盐和NO的水平。此外,添加自由基清除剂(TROLOX和羧基-PTIO)可中和铁对拉莫斯细胞的影响,而向细胞中添加NO供体或过氧化氢(H2O2)会产生部分模拟铁添加诱导效应的作用。总的来说,我们的结果表明自由基作为效应物参与了体外观察到的铁对BL细胞的特异性生长抑制。