alpha-Mangostin Reduced ER Stress-mediated Tumor Growth through Autophagy Activation
Immune Network
; : 253-260, 2012.
Article
em En
| WPRIM
| ID: wpr-20067
Biblioteca responsável:
WPRO
ABSTRACT
alpha-Mangostin is a xanthon derivative contained in the fruit hull of mangosteen (Garcinia mangostana L.), and the administration of alpha-Mangostin inhibited the growth of transplanted colon cancer, Her/CT26 cells which expressed Her-2/neu as tumor antigen. Although alpha-Mangostin was reported to have inhibitory activity against sarco/endoplasmic reticulum Ca2+ ATPase like thapsigargin, it showed different activity for autophagy regulation. In the current study, we found that alpha-Mangostin induced autophagy activation in mouse intestinal epithelial cells, as GFP-LC3 transgenic mice were orally administered with 20 mg/kg of alpha-Mangostin daily for three days. However, the activation of autophagy by alpha-Mangostin did not significantly increase OVA-specific T cell proliferation. As we assessed ER stress by using XBP-1 reporter system and phosphorylation of eIF2alpha, thapsigargin-induced ER stress was significantly reduced by alpha-Mangostin. However, coadministration of thapsigargin with alpha-Mangostin completely blocked the antitumor activity of alpha-Mangostin, suggesting ER stress with autophagy blockade accelerated tumor growth in mouse colon cancer model. Thus the antitumor activity of alpha-Mangostin can be ascribable to the autophagy activation rather than ER stress induction.
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Texto completo:
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Índice:
WPRIM
Assunto principal:
Fosforilação
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Retículo
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Autofagia
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Camundongos Transgênicos
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ATPases Transportadoras de Cálcio
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Neoplasias do Colo
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Tapsigargina
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Transplantes
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Garcinia mangostana
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Xantonas
Limite:
Animals
Idioma:
En
Revista:
Immune Network
Ano de publicação:
2012
Tipo de documento:
Article