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Involvement of endoplasmic reticulum stress and activation of MAP kinases in B-lapachone-induced human prostate cancer cell apoptosis

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dc.contributor.authorLien, Yi-Chenes
dc.contributor.authorKung, Hsiu-Nies
dc.contributor.authorLu, Kuo-Shyan
dc.contributor.authorJeng, Chung-Jiuan
dc.contributor.authorChau, Yat-Pang
dc.date.accessioned2013-01-22T10:04:33Z
dc.date.available2013-01-22T10:04:33Z
dc.date.issued2008
dc.description.abstractß-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.es
dc.formatapplication/pdfes
dc.format.extent10es
dc.identifier.issn0213-3911es
dc.identifier.urihttp://hdl.handle.net/10201/29849
dc.languageenges
dc.publisherMurcia : F. Hernándezes
dc.relation.ispartofHistology and histopathologyes
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectEndoplasmic reticulumes
dc.subjectStresses
dc.subject.other576 - Biología celular y subcelular. Citologíaes
dc.titleInvolvement of endoplasmic reticulum stress and activation of MAP kinases in B-lapachone-induced human prostate cancer cell apoptosises
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.23,nº11 (2008)