Nox4-dependent ROS modulation by amino endoperoxides to induce apoptosis in cancer cells.
Cell Death Dis
; 4: e552, 2013 Mar 21.
Article
em En
| MEDLINE
| ID: mdl-23519121
ABSTRACT
Tumor metastasis is the main cause of death in cancer patients. Anoikis resistance is one critical malefactor of metastatic cancer cells to resist current clinical chemotherapeutic treatments. Although endoperoxide-containing compounds have long been suggested as anticancer drugs, few have been clinically employed due to their instability, complex synthesis procedure or low tumor cell selectivity. Herein, we describe a one-pot strategy to synthesize novel amino endoperoxides and their derivatives with good yields and stabilities. In vitro cell-based assays revealed that 4 out of the 14 amino endoperoxides selectively induce metastatic breast carcinoma cells but not normal breast cells to undergo apoptosis, in a dose-dependent manner. Mechanistic studies showed that the most potent amino endoperoxide, 4-Me, is selective for cancer cells expressing a high level of Nox4. The anticancer effects are further shown to be associated with reduced O2(-)H2O2 ratio and increased ·OH level in the cancerous cells. Animal study showed that 4-Me impairs orthotopic breast tumor growth as well as tumor cell metastasis to lymph nodes. Altogether, our study suggests that anticancer strategies that focus on redox-based apoptosis induction in tumors are clinically viable.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Peróxidos
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Neoplasias da Mama
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Carcinoma
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NADPH Oxidases
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Antineoplásicos
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Singapura