Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells.

Details

Serval ID
serval:BIB_58E9736BD7FF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells.
Journal
International Journal of Urology
Author(s)
Tsapakidis K., Vlachostergios P.J., Voutsadakis I.A., Befani C.D., Patrikidou A., Hatzidaki E., Daliani D.D., Moutzouris G., Liakos P., Papandreou C.N.
ISSN
1442-2042 (Electronic)
ISSN-L
0919-8172
Publication state
Published
Issued date
2012
Volume
19
Number
6
Pages
565-574
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
pdf "Original Article: Laboratory Investigation"
Abstract
Objectives:  Neuropeptides are important signal initiators in advanced prostate cancer, partially acting through activation of nuclear factor kappa B. Central to nuclear factor kappa B regulation is the ubiquitin-proteasome system, pharmacological inhibition of which has been proposed as an anticancer strategy. We investigated the putative role of the proteasome inhibitor bortezomib in neuropeptides signaling effects on prostate cancer cells. Methods:  Human prostate cancer cell lines, LNCaP and PC-3, were used to examine cell proliferation, levels of proapoptotic (caspase-3, Bad) and cell cycle regulatory proteins (p53, p27, p21), as well as total and phosphorylated Akt and p44/42 mitogen-activated protein kinase proteins. Furthermore, 20S proteasome activity, subcellular localization of nuclear factor kappa B and transcription of nuclear factor kappa B target genes, interleukin-8 and vascular endothelial growth factor, were assessed. Results:  Neuropeptides (endothelin-1, bombesin) increased cell proliferation, whereas bortezomib decreased proliferation and induced apoptosis, an effect maintained after cotreatment with neuropeptides. Bad, p53, p21 and p27 were downregulated by neuropeptides in PC-3, and these effects were reversed with the addition of bortezomib. Neuropeptides increased proteasomal activity and nuclear factor kappa B levels in PC-3, and these effects were prevented by bortezomib. Interleukin-8 and vascular endothelial growth factor transcripts were induced after neuropeptides treatment, but downregulated by bortezomib. These results coincided with the ability of bortezomib to reduce mitogen-activated protein kinase signaling in both cell lines. Conclusions:  These findings are consistent with bortezomib-mediated abrogation of neuropeptides-induced proliferative and antiapoptotic signaling. Thus, the effect of the drug on the neuropeptides axis needs to be further investigated, as neuropeptide action in prostate cancer might entail involvement of the proteasome.
Pubmed
Web of science
Create date
14/06/2012 17:26
Last modification date
20/08/2019 14:12
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