Discovery of the tryptanthrin-derived indoloquinazoline as an anti-breast cancer agent via ERK/JNK activation.
Environ Toxicol
; 39(6): 3710-3720, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38511855
ABSTRACT
Tryptanthrin, an alkaloid applied in traditional Chinese medicine, exhibits a variety of pharmacological activities. This study aimed to investigate the anti-tumor activity of the tryptanthrin derivative (8-cyanoindolo[2,1-b]quinazoline-6,12-dione [CIQ]) in breast cancer cells. In both MDA-MB-231 and MCF-7 breast cancer cells, CIQ inhibited cell viability and promoted caspase-dependent apoptosis. At the concentration- and time-dependent ways, CIQ increased the levels of p-ERK, p-JNK, and p-p38 in breast cancer cells. We found that exposure to the JNK inhibitor or the ERK inhibitor partially reversed CIQ's viability. We also observed that CIQ increased reactive oxygen species (ROS) generation, and upregulated the phosphorylation and expression of H2AX. However, the pretreatment of the antioxidants did not protect the cells against CIQ's effects on cell viability and apoptosis, which suggested that ROS does not play a major role in the mechanism of action of CIQ. In addition, CIQ inhibited the invasion of MDA-MB-231 cells and decreased the expression of the prometastatic factors (MMP-2 and Snail). These findings demonstrated that the possibility of this compound to show promise in playing an important role against breast cancer.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Neoplasias da Mama
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Sobrevivência Celular
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Apoptose
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Antineoplásicos
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article