Endothelin-receptor antagonists are proapoptotic and antiproliferative in human colon cancer cells.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_0089B0AD8A17
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Endothelin-receptor antagonists are proapoptotic and antiproliferative in human colon cancer cells.
Journal
British journal of cancer
Author(s)
Peduto Eberl L., Bovey R., Juillerat-Jeanneret L.
ISSN
0007-0920 (Print)
ISSN-L
0007-0920
Publication state
Published
Issued date
10/03/2003
Peer-reviewed
Oui
Volume
88
Number
5
Pages
788-795
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Endothelin (ET)-1 can act as an autocrine/paracrine growth factor or an antiapoptotic factor in human cancers. To study the role of ET-1 in human colon cancer, proliferation and apoptosis of colon carcinoma cells was investigated using human HT-29 and SW480 colon carcinoma cells. ET-1 was secreted by these cells. Treatment of cells with bosentan, a dual ET(A/B)-receptor antagonist, decreased cell number. Inhibition of DNA synthesis by bosentan was observed only in the presence of serum. Exogenously added ET-1 did not increase DNA synthesis in serum-deprived cells. SW480 cells were sensitive and HT-29 cells were resistant to FasL-induced apoptosis. Bosentan sensitised resistant HT-29 cells to FasL-induced, caspase-mediated apoptosis, but not to TNF-alpha-induced apoptosis. Bosentan and/or FasLigand (FasL) did not modulate the expression of caspase-8 or FLIP. Bosentan sensitisation to apoptosis was reversed by low concentrations (10(-13)-10(-10) M), but not by high concentrations (10(-9)-10(-7) M) of ET-1. These results suggest that the binding of ET-1 to high-affinity sites inhibits FasL-induced apoptosis, while the binding of either ET-1 or receptor antagonists to low-affinity sites promotes FasL-induced apoptosis. In conclusion, endothelin signalling pathways do not induce human colon cancer cell proliferation, but are survival signals controling resistance to apoptosis.

Keywords
Apoptosis/drug effects, Base Sequence, Caspase 8, Caspase 9, Caspases/metabolism, Cell Division/drug effects, Colonic Neoplasms/metabolism, Colonic Neoplasms/pathology, DNA Primers, Endothelin Receptor Antagonists, Endothelin-1/metabolism, Flow Cytometry, Humans, Immunohistochemistry, Reverse Transcriptase Polymerase Chain Reaction, Sulfonamides/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 18:33
Last modification date
20/08/2019 12:22
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