Please use this identifier to cite or link to this item: http://hdl.handle.net/10201/29849

Title: Involvement of endoplasmic reticulum stress and activation of MAP kinases in B-lapachone-induced human prostate cancer cell apoptosis
Issue Date: 2008
Publisher: Murcia : F. Hernández
ISSN: 0213-3911
Related subjects: 576 - Biología celular y subcelular. Citología
Keywords: Endoplasmic reticulum
Stress
Abstract: 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.
Primary author: Lien, Yi-Chen
Kung, Hsiu-Ni
Lu, Kuo-Shyan
Jeng, Chung-Jiuan
Chau, Yat-Pang
Published in: Histology and histopathology
URI: http://hdl.handle.net/10201/29849
Document type: info:eu-repo/semantics/article
Number of pages / Extensions: 10
Rights: info:eu-repo/semantics/openAccess
Appears in Collections:Vol.23,nº11 (2008)



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