Free radicals act as effectors in the growth inhibition and apoptosis of iron-treated Burkitt's lymphoma cells.
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.
Habel
Marie-Eve
ME
Héma-Québec, Recherche et Développement, 1009, Département de Biochimie et Microbiologie, Université Laval, route du Vallon, Sainte-Foy, Qué., Canada G1V 5C3.
Jung
Daniel
D
D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D005290:Ferric Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
D005290:Ferric Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D016271:Proto-Oncogene Proteins c-myc; D009569:Nitric Oxide; C025314:ferric citrate; D006861:Hydrogen Peroxide; D007501:Iron