Arsenic Trioxide Induces A poptosis in Human Colorectal Adenocarcinoma HT-29 Cells Through ROS / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
; : 54-60, 2006.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-43439
Biblioteca responsável:
WPRO
ABSTRACT
PURPOSE:
Treatment with arsenic trioxide (As2O3) results in a wide range of cellular effects that includes induction of apoptosis, inhibition of cell growth, promotion or inhibition of cellular differentiation, and inhibition of angiogenesis through a variety of mechanisms. The mechanisms of As2O3-induced cell death have been mainly studied in hematological cancers, and those mechanisms in solid cancers have yet to be clearly defined. In this study, the mechanisms by which As2O3 induces apoptosis in human colorectal adenocarcinoma HT-29 cells were investigated. MATERIALS ANDMETHODS:
To examine the levels of apoptosis, HT-29 cells were treated with As2O3 and then we measured the percentage of Annexin V binding cells, the amount of ROS production and the mitochondrial membrane potential. Western blot analysis was performe to identify the activated caspases after As2O3 exposure, and we compared the possible target molecules of apoptosis. As2O3 treatment induced the loss of the mitochondrial membrane potential and an increase of ROS, as well as activation of caspase-3, -7, -9 and -10.RESULTS:
As2O3 induced apoptosis via the production of reactive oxygen species and the loss of the mitochondrial membrane potential. As2O3 induced the activation of caspase-3, -7, -9 and -10. Furthermore, As2O3 treatment downregulates the Mcl-1 and Bcl-2 expressions, and the release of cytochrome c and an apoptosis-inducing factor (AIF). Pretreating the HT-29 cells with N-acetyl-L-cysteine, which is a thiol-containing antioxidant, inhibited the As2O3- Induced Apoptosis and Caspase Activation.CONCLUSION:
Taken together, these results suggest that the generation of reactive oxygen species (ROS) by As2O3 might play an important role in the regulation of As2O3-induced apoptosis. This cytotoxicity is mediated through a mitochondria-dependent apoptotic signal pathway in HT-29 cells.
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Arsênio
/
Acetilcisteína
/
Adenocarcinoma
/
Transdução de Sinais
/
Western Blotting
/
Morte Celular
/
Espécies Reativas de Oxigênio
/
Apoptose
/
Anexina A5
/
Células HT29
Tipo de estudo:
Estudo prognóstico
Limite:
Humanos
Idioma:
Inglês
Revista:
Cancer Research and Treatment
Ano de publicação:
2006
Tipo de documento:
Artigo