Mahanine synergistically enhances cytotoxicity of 5-fluorouracil through ROS-mediated activation of PTEN and p53/p73 in colon carcinoma.
Apoptosis
; 19(1): 149-64, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24052409
ABSTRACT
5-Fluorouracil (5-FU) alone or in combination with other drugs is the main basis of chemotherapeutic treatment in colorectal cancer although patients with microsatellite instability generally show resistance to 5-FU treatment. The present investigation is focussed on the mechanistic insight of a pure herbal carbazole alkaloid, mahanine, as a single or in combination with 5-FU in colon cancer. We demonstrated that mahanine-induced apoptosis involved reactive oxygen species (ROS)-mediated nuclear accumulation of PTEN and its interaction with p53/p73. Mahanine and 5-FU in combination exerted synergistic inhibitory effect on cell viability. This combination also enhanced ROS production, increased tumour suppressor proteins and suppressed chemo-migration. Taken together, our results revealed that mahanine can be a potential chemotherapeutic agent with efficacy to reduce the concentration of toxic 5-FU in colon cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carbazóis
/
Proteínas Nucleares
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Carcinoma
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Proteína Supressora de Tumor p53
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Espécies Reativas de Oxigênio
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Neoplasias do Colo
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Proteínas Supressoras de Tumor
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Proteínas de Ligação a DNA
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PTEN Fosfo-Hidrolase
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Fluoruracila
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article