J Cancer
2021; 12(19):5693-5711.
doi:10.7150/jca.59769 This issueCite
Research Paper
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/β-catenin pathway in glioma
Rosa Angélica Castillo-Rodríguez1*, Guadalupe Palencia2*, Isabel Anaya-Rubio2, Juan Carlos Gallardo- Pérez3, Dolores Jiménez-Farfán4, Ángel Escamilla-Ramírez2,5, Sergio Zavala-Vega6, Arturo Cruz-Salgado2, Claudia Cervantes-Rebolledo7, Isabel Gracia-Mora8, Lena Ruiz-Azuara9, Cristina Trejo-Solis2✉
1. CONACYT-Instituto Nacional de Pediatría, Ciudad de México 04530, México 2. Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México 14269, Tlalpan, México 3. Departamento de Bioquímica, Instituto Nacional de Cardiología, Ciudad de México 14080, Tlalpan, México 4. Laboratorio de Inmunología, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, Ciudad de México 04510, México 5. Hospital Regional de Alta Especialidad de Oaxaca, Secretaria de Salud, C.P. 71256 Oaxaca, México 6. Departamento de Patología, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México 14269, Tlalpan, México 7. Universidad de Ixtlahuaca-UICUI, México, Estado de México 8. Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Investigación Científica 70, Ciudad de México 04510, México 9. Facultad de Química, Departamento de Química Inorgánica y Nuclear, Universidad Nacional Autónoma de México, Ciudad de México 04510, México * These authors contributed equally to this work.
✉ Corresponding author: cristina.trejoedu.mx, Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, SSA, México City, 14269, México.
Citation:
Castillo-Rodríguez RA, Palencia G, Anaya-Rubio I, Pérez JCG, Jiménez-Farfán D, Escamilla-Ramírez Á, Zavala-Vega S, Cruz-Salgado A, Cervantes-Rebolledo C, Gracia-Mora I, Ruiz-Azuara L, Trejo-Solis C. 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/β-catenin pathway in glioma. J Cancer 2021; 12(19):5693-5711. doi:10.7150/jca.59769. https://www.jcancer.org/v12p5693.htm
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 GSK3β, activating JNK and ERK, and promoting the nuclear accumulation of β-catenin. The inhibition of ROS generation by N-acetyl-l-cysteine not only recovered cell migration and viability, but also reduced β-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.
Castillo-Rodríguez, R.A., Palencia, G., Anaya-Rubio, I., Pérez, J.C.G., Jiménez-Farfán, D., Escamilla-Ramírez, Á., Zavala-Vega, S., Cruz-Salgado, A., Cervantes-Rebolledo, C., Gracia-Mora, I., Ruiz-Azuara, L., Trejo-Solis, C. (2021). 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/β-catenin pathway in glioma. Journal of Cancer, 12(19), 5693-5711. https://doi.org/10.7150/jca.59769.
ACS
Castillo-Rodríguez, R.A.; Palencia, G.; Anaya-Rubio, I.; Pérez, J.C.G.; Jiménez-Farfán, D.; Escamilla-Ramírez, Á.; Zavala-Vega, S.; Cruz-Salgado, A.; Cervantes-Rebolledo, C.; Gracia-Mora, I.; Ruiz-Azuara, L.; Trejo-Solis, C. 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/β-catenin pathway in glioma. J. Cancer 2021, 12 (19), 5693-5711. DOI: 10.7150/jca.59769.
NLM
Castillo-Rodríguez RA, Palencia G, Anaya-Rubio I, Pérez JCG, Jiménez-Farfán D, Escamilla-Ramírez Á, Zavala-Vega S, Cruz-Salgado A, Cervantes-Rebolledo C, Gracia-Mora I, Ruiz-Azuara L, Trejo-Solis C. 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/β-catenin pathway in glioma. J Cancer 2021; 12(19):5693-5711. doi:10.7150/jca.59769. https://www.jcancer.org/v12p5693.htm
CSE
Castillo-Rodríguez RA, Palencia G, Anaya-Rubio I, Pérez JCG, Jiménez-Farfán D, Escamilla-Ramírez Á, Zavala-Vega S, Cruz-Salgado A, Cervantes-Rebolledo C, Gracia-Mora I, Ruiz-Azuara L, Trejo-Solis C. 2021. 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/β-catenin pathway in glioma. J Cancer. 12(19):5693-5711.
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