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10 mars 2003
- doi: 10.1038/sj.bjc.6600810
- issn: 0007-0920
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Opponents Foes Enemies (Persons) Antagonists Adversaries Deoxyribonucleic acid TNA (Nucleic acid) Desoxyribonucleic acid Thymonucleic acid Colon cancer Colorectal cancer Carcinoma Cancers Malignancy (Cancer) Malignant tumorsCiter ce document
L. Peduto Eberl et al., « Endothelin-receptor antagonists are proapoptotic and antiproliferative in human colon cancer cells. », Serveur académique Lausannois, ID : 10.1038/sj.bjc.6600810
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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.