Cas IIgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspase-dependent and caspase-independent mechanisms

Cristina Trejo-Solís, Guadalupe Palencia, Sergio Zúñiga, Andrea Rodríguez-Ropon, Laura Osorio-Rico, Sanchez Torres Luvia, Isabel Gracia-Mora, Lucrecia Marquez-Rosado, Aurora Sánchez, Miguel E. Moreno-García, Arturo Cruz, María Elena Bravo-Gómez, Lena Ruiz-Ramírez, Sara Rodríguez-Enriquez, Julio Sotelo

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118 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)563-574
Number of pages12
JournalNeoplasia
Volume7
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Apoptosis-inducing factor
  • Casiopeina II-gly
  • Glioma C6 cells
  • Reactive oxygen species

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