TY - JOUR
T1 - Cas IIgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspase-dependent and caspase-independent mechanisms
AU - Trejo-Solís, Cristina
AU - Palencia, Guadalupe
AU - Zúñiga, Sergio
AU - Rodríguez-Ropon, Andrea
AU - Osorio-Rico, Laura
AU - Luvia, Sanchez Torres
AU - Gracia-Mora, Isabel
AU - Marquez-Rosado, Lucrecia
AU - Sánchez, Aurora
AU - Moreno-García, Miguel E.
AU - Cruz, Arturo
AU - Bravo-Gómez, María Elena
AU - Ruiz-Ramírez, Lena
AU - Rodríguez-Enriquez, Sara
AU - Sotelo, Julio
N1 - Funding Information:
Abbreviations: Cas IIgly, Casiopeina IIgly; PCD, programmed cell death; AIF, apoptosis-inducing factor; ROS, reactive oxygen species; NAC, N-acetyl-L-cystein; SOD, superoxide dismutase; GPx, glutathione peroxidase; MTT, 3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; FACS, fluorescence-activated cell sorter; NBT, 4-nitro blue tetrazolium chloride; BCIP, 5-bromide-4-chloride-3-indolyl-phosphate 4-toluidine salt; TUNEL, terminal deoxynucleotidyl transferase – mediated nick end labeling; R123, rhodamine 123; cyt c, cytochrome c; Endo G, endonuclease G; DCFH-DA, 2V,7V-dichlorofluorescein diacetate; DCF, 2V, 7V-dichlorofluorescein; TBARS, thiobarbituric acid reactive substances; PMSF, phenymethyl-sulfonyl fluoride; PCNA, proliferating cell nuclear antigen; PAGE, polyacrylamide gel electrophoresis; ECL, enhanced chemiluminescence; SGOT, aspartate transaminase; SGPT, alanine transaminase; GGT, gamma glutamyl transferase Address all correspondence to: Dr. Cristina Trejo-Solís, Departamento de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Insurgentes Sur 3877, Mexico, DF 14269, México. E-mail: trejosolis@yahoo.com.mx 1This work was supported by CONACyT grants U41997-MA1 and C01-7677-Salud, 2002. Received 8 September 2004; Revised 18 January 2005; Accepted 18 January 2005.
PY - 2005/6
Y1 - 2005/6
N2 - 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 Co-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.
AB - 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 Co-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.
KW - Apoptosis
KW - Apoptosis-inducing factor
KW - Casiopeina II-gly
KW - Glioma C6 cells
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=22044442732&partnerID=8YFLogxK
U2 - 10.1593/neo.04607
DO - 10.1593/neo.04607
M3 - Artículo
SN - 1522-8002
VL - 7
SP - 563
EP - 574
JO - Neoplasia
JF - Neoplasia
IS - 6
ER -