title: Casiopeína IIgly induced cytotoxicity to HeLa cells depletes the levels of reduced glutathione and is prevented by dimethyl sulfoxide.
abstract: The newly synthesized copper coordination compound Casiopeína IIgly (Cas IIgly) is a promising alternative drug in the treatment of cancer, since it has shown cytotoxicity and genotoxicity in different tumour models. Given its enhanced effects after ascorbic acid-mediated copper reduction, Cas IIgly's activity is thought to be related to oxidative damage. In the present work, oxidized Cas IIgly failed to induce cytosolic oxidative damage in HeLa cells (only 0.9% of the cell population), and in 2.3% of the treated cells when previously reduced, as evaluated through the oxidation of dihydrorhodamine 123 (DHR 123). However, it showed cytotoxicity, since HeLa cells treated with 10-80 microg/mL Cas IIgly proliferated only at 30% of their normal rate, and at 15% when treated with reduced Cas IIgly. This cytotoxicity is strongly abolished in the presence of the hydroxyl scavenger dimethyl sulfoxide. The decrease, from 3994 to 530 nanograms of reduced glutathione (GSH) per million cells after treatment with 80 microg/mL Casiopeína IIgly, indicates that this drug causes the expenditure of this naturally occurring antioxidant. These results altogether suggest that, albeit Cas IIgly induced cytotoxicity is not related to cytosolic DHR 123 oxidation, it may be related to oxidative damage.
authors.affiliation: Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), México D.F. CP 04510, Mexico. ranapez@hotmail.com
authors.forename: Radamés
authors.initials: R
authors.lastname: Alemón-Medina
authors.forename: José Luis
authors.initials: JL
authors.lastname: Muñoz-Sánchez
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Azuara
authors.forename: Isabel
authors.initials: I
authors.lastname: Gracia-Mora
mesh_terms: D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000648:ultrastructure; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005978:Glutathione / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009942:Organometallic Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D020112:Rhodamine 123
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; C505569:casiopeina II-glycine; D020112:Rhodamine 123; D005978:Glutathione; D004121:Dimethyl Sulfoxide