LDHA Suppression Altering Metabolism Inhibits Tumor Progress by an Organic Arsenical.
Int J Mol Sci
; 20(24)2019 Dec 11.
Article
em En
| MEDLINE
| ID: mdl-31835667
ABSTRACT
Based on the potential therapeutic value in targeting metabolism for the treatment of cancer, an organic arsenical PDT-BIPA was fabricated, which exerted selective anti-cancer activity in vitro and in vivo via targeting lactate dehydrogenase A (LDHA) to remodel the metabolic pathway. In details, the precursor PDT-BIPA directly inhibited the function of LDHA and converted the glycolysis to oxidative phosphorylation causing ROS burst and mitochondrial dysfunction. PDT-BIPA also altered several gene expression, such as HIF-1α and C-myc, to support the metabolic remodeling. All these changes lead to caspase family-dependent cell apoptosis in vivo and in vitro without obvious side effect. Our results provided this organic arsenical precursor as a promising anticancer candidate and suggested metabolism as a target for cancer therapies.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Compostos Orgânicos
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Arsenicais
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Progressão da Doença
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Lactato Desidrogenase 5
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Neoplasias
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article