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Título: | Involvement of endoplasmic reticulum stress and activation of MAP kinases in B-lapachone-induced human prostate cancer cell apoptosis |
Fecha de publicación: | 2008 |
Editorial: | Murcia : F. Hernández |
ISSN: | 0213-3911 |
Materias relacionadas: | 576 - Biología celular y subcelular. Citología |
Palabras clave: | Endoplasmic reticulum Stress |
Resumen: | ß-Lapachone, an o-naphthoquinone, induces various carcinoma cells to undergo apoptosis, but the mechanism is poorly understood. In the present study, we found that the ß-lapachone-induced apoptosis of DU145 human prostate carcinoma cells was associated with endoplasmic reticulum (ER) stress, as shown by increased intracellular calcium levels and induction of GRP-78 and GADD-153 proteins, suggesting that the endoplasmic reticulum is a target of ß-lapachone. ß- Lapachone-induced DU145 cell apoptosis was dosedependent and accompanied by cleavage of procaspase- 12 and phosphorylation of p38, ERK, and JNK, followed by activation of the executioner caspases, caspase-7 and calpain. However, pretreatment with the general caspase inhibitor, z-VAD-FMK, or calpain inhibitors, including ALLM or ALLN, failed to prevent ß-lapachone-induced apoptotic cell death. Blocking the enzyme activity of NQO1 with dicoumarol, a known NQO1 inhibitor, or preventing an increase in intracellular calcium levels using BAPTA-AM, an intracellular calcium chelator, substantially inhibited MAPK phosphorylation, abolished the activation of calpain, caspase-12 and caspase-7, and provided significant protection of ßlapachone- treated cells. These findings show that ßlapachone- induced ER stress and MAP kinase phosphorylation is a novel signaling pathway underlying the molecular mechanism of the anticancer effect of ßlapachone. |
Autor/es principal/es: | Lien, Yi-Chen Kung, Hsiu-Ni Lu, Kuo-Shyan Jeng, Chung-Jiuan Chau, Yat-Pang |
Forma parte de: | Histology and histopathology |
URI: | http://hdl.handle.net/10201/29849 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 10 |
Derechos: | info:eu-repo/semantics/openAccess |
Aparece en las colecciones: | Vol.23,nº11 (2008) |
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Fichero | Descripción | Tamaño | Formato | |
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Involvement of endoplasmic reticulum stress and activation of MAP kinases in B-lapachone-induced human prostate cancer cell apoptosis.pdf | 2,51 MB | Adobe PDF | Visualizar/Abrir |
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