期刊
JOURNAL OF CANCER
卷 12, 期 19, 页码 5693-5711出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.59769
关键词
glioma cells; Cas III-La; reactive oxygen species; GSK3 beta; beta-catenin; apoptosis
类别
资金
- DGAPA-PAPIIT Projects [221616, 223720]
- National Institute of Pediatrics [016/2019]
- Catedras-CONACyT [1059]
Gliomas, particularly glioblastoma multiforme (GBM), are highly aggressive neoplasms affecting the central nervous system. The copper coordination compound Casiopeina III-La (Cas III-La) has shown promising anti-proliferative, pro-apoptotic, and anti-invasive effects on human U373 MG cells, making it a potential agent for treating GBM.
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.
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