title: Cas IIgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspase-dependent and caspase-independent mechanisms.
abstract: In this work, we investigated the effects of Casiopeina II-gly (Cas IIgly)--a new copper compound exhibiting antineoplastic activity--on glioma C6 cells under both in vitro and in vivo conditions, as an approach to identify potential therapeutic agents against malignant glioma. The exposure of C6 cells to Cas IIgly significantly inhibited cell proliferation, increased reactive oxygen species (ROS) formation, and induced apoptosis in a dose-dependent manner. In cultured C6 cells, Cas IIgly caused mitochondrio-nuclear translocation of apoptosis induction factor (AIF) and endonuclease G at all concentrations tested; in contrast, fragmentation of nucleosomal DNA, cytochrome c release, and caspase-3 activation were observed at high concentrations. Administration of N-acetyl-L-cystein, an antioxidant, resulted in significant inhibition of AIF translocation, nucleosomal DNA fragmentation, and caspase-3 activation induced by Cas IIgly. These results suggest that caspase-dependent and caspase-independent pathways both participate in apoptotic events elicited by Cas IIgly. ROS formation induced by Cas IIgly might also be involved in the mitochondrio-nuclear translocation of AIF and apoptosis. In addition, treatment of glioma C6-positive rats with Cas IIgly reduced tumor volume and mitotic and cell proliferation indexes, and increased apoptotic index. Our findings support the use of Cas IIgly for the treatment of malignant gliomas.
authors.affiliation: Departamento de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía, SSA, Mexico, DF 14269, Mexico. trejosolis@yahoo.com.mx
authors.forename: Cristina
authors.initials: C
authors.lastname: Trejo-Solís
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Palencia
authors.forename: Sergio
authors.initials: S
authors.lastname: Zúñiga
authors.forename: Andrea
authors.initials: A
authors.lastname: Rodríguez-Ropon
authors.forename: Laura
authors.initials: L
authors.lastname: Osorio-Rico
authors.forename: Sanchez Torres
authors.initials: ST
authors.lastname: Luvia
authors.forename: Isabel
authors.initials: I
authors.lastname: Gracia-Mora
authors.forename: Lucrecia
authors.initials: L
authors.lastname: Marquez-Rosado
authors.forename: Aurora
authors.initials: A
authors.lastname: Sánchez
authors.forename: Miguel E
authors.initials: ME
authors.lastname: Moreno-García
authors.forename: Arturo
authors.initials: A
authors.lastname: Cruz
authors.forename: María Elena
authors.initials: ME
authors.lastname: Bravo-Gómez
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Ramírez
authors.forename: Sara
authors.initials: S
authors.lastname: Rodríguez-Enriquez
authors.forename: Julio
authors.initials: J
authors.lastname: Sotelo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D021581:Active Transport, Cell Nucleus; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008564:Membrane Potentials; D008928:Mitochondria / Q000473:pathology; D009707:Nucleosomes / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013347:Subcellular Fractions
chemical_list: D000975:Antioxidants; D002843:Chromatin; D009707:Nucleosomes; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; C505569:casiopeina II-glycine; D003300:Copper; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D000111:Acetylcysteine