Anti-proliferative, pro-apoptotic and anti-invasive effect of the copper coordination compound Cas III-La through the induction of reactive oxygen species and regulation of Wnt/beta-catenin pathway in glioma
Por:
Angelica Castillo-Rodriguez, Rosa, Palencia, Guadalupe, Anaya-Rubio, Isabel, Carlos Gallardo-Perez, Juan, Jimenez-Farfan, Dolores, Escamilla-Ramirez, Angel, Zavala-Vega, Sergio, Cruz-Salgado, Arturo, Cervantes-Rebolledo, Claudia, Gracia-Mora, Isabel, Ruiz-Azuara, Lena, Trejo-Solis, Cristina
Publicada:
1 ene 2021
Categoría:
Oncology
Resumen:
Gliomas are the most aggressive neoplasms that affect the central
nervous system, being glioblastoma multiforme (GBM) the most malignant.
The resistance of GBM to therapies is attributed to its high rate of
cell proliferation, angiogenesis, invasion, and resistance to apoptosis;
thus, finding alternative therapeutic approaches is vital. In this work,
the anti-proliferative, pro-apoptotic, and anti-invasive effect of the
copper coordination compound Casiopeina III-La (Cas III-La) on human
U373 MG cells was determined in vitro and in vivo. Our results indicate
that Cas III-La exerts an anti-proliferative effect, promoting apoptotic
cell death and inactivating the invasive process by generating reactive
oxygen species (ROS), inactivating GSK3 beta, activating JNK and ERK,
and promoting the nuclear accumulation of beta-catenin. The inhibition
of ROS generation by N-acetyl-l-cysteine not only recovered cell
migration and viability, but also reduced beta-catenin accumulation and
JNK and ERK activation. Additionally, Cas III-La significantly reduced
tumor volume, cell proliferation and mitotic indices, and increased the
apoptotic index in mice xenotransplanted with U373 glioma cells. Thus,
Cas III-La is a promising agent to treat GBM.
Filiaciones:
Trejo-Solis, C (Corresponding Author), Inst Nacl Neurol & Neurocirug, Lab Expt Enfermedades Neurodegenerat, Tlalpan 14269, Mexico. Trejo-Solis, C (Corresponding Author), Inst Nacl Neurol & Neurocirug, Lab Expt Enfermedades Neurodegenerat, Mexico City 14269, DF, Mexico. Angelica Castillo-Rodriguez, Rosa, CONACYT Inst Nacl Pediatria, Ciudad Mexico 04530, Cdmx, Mexico. Palencia, Guadalupe
Open Access
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