STAT3 Pathways Contribute to ß-HCH Interference with Anticancer Tyrosine Kinase Inhibitors.
Int J Mol Sci
; 25(11)2024 Jun 04.
Article
em En
| MEDLINE
| ID: mdl-38892372
ABSTRACT
Organochlorine pesticides (OCPs) are a class of environmentally persistent and bioaccumulative pollutants. Among these, ß-hexachlorocyclohexane (ß-HCH) is a byproduct of lindane synthesis, one of the most worldwide widespread pesticides. ß-HCH cellular mechanisms inducing chemical carcinogenesis correspond to many of those inducing chemoresistance, in particular, by the activation of signal transducer and activator of transcription 3 (STAT3) signaling pathways. For this purpose, four cell lines, representative of breast, lung, prostate, and hepatocellular cancers, were treated with ß-HCH, specific tyrosine kinase inhibitors (TKIs), and a STAT3 inhibitor. All cell samples were analyzed by a viability assay, immunoblotting analysis, a wound-healing assay, and a colony formation assay. The results show that ß-HCH reduces the efficacy of TKIs. The STAT3 protein, in this context, plays a central role. In fact, by inhibiting its activity, the efficacy of the anticancer drug is restored. Furthermore, this manuscript aimed to draw the attention of the scientific and socio-healthcare community to the issue of prolonged exposure to contaminants and their impact on drug efficacy.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hexaclorocicloexano
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Transdução de Sinais
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Inibidores de Proteínas Quinases
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Fator de Transcrição STAT3
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article