Effective killing of cancer cells and regression of tumor growth by K27 targeting sulfiredoxin.
Free Radic Biol Med
; 101: 384-392, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27825965
ABSTRACT
Cancer cells have been suggested to be more susceptible to oxidative damages and highly dependent on antioxidant capacity in comparison with normal cells, and thus targeting antioxidant enzymes has been a strategy for effective cancer treatment. Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of sulfinylated peroxiredoxins and thereby reactivates them. In this study we developed a Srx inhibitor, K27 (N-[7-chloro-2-(4-fluorophenyl)-4-quinazolinyl]-N-(2-phenylethyl)-ß-alanine), and showed that it induces the accumulation of sulfinylated peroxiredoxins and oxidative stress, which leads to mitochondrial damage and apoptotic death of cancer cells. The effects of K27 were significantly reversed by ectopic expression of Srx or antioxidant N-acetyl cysteine. In addition, K27 led to preferential death of tumorigenic cells over non-tumorigenic cells, and suppressed the growth of xenograft tumor without acute toxicity. Our results suggest that targeting Srx might be an effective therapeutic strategy for cancer treatment through redox-mediated cell death.
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Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Beta-Alanina
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Espécies Reativas de Oxigênio
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Adenocarcinoma Bronquioloalveolar
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Inibidores Enzimáticos
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Oxirredutases atuantes sobre Doadores de Grupo Enxofre
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Neoplasias Pulmonares
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Antineoplásicos
Idioma:
En
Revista:
Free Radic Biol Med
Ano de publicação:
2016
Tipo de documento:
Article