These results suggest that ET-receptor antagonists have binding sites different from the cell-surface ETA/B receptors, and also suggest that ET peptides and antagonists, including bosentan, BQ123 or BQ788, have two binding sites in human colon cancer cells: a high-affinity binding site, whose occupancy by ET-1 protects against FasL-induced apoptosis, and a low-affinity binding site, whose occupancy either by ET-1 or receptor antagonists sensitises cells to apoptosis and whose exact nature is presently not defined. This evidence concerns the gene EDN1 and malignant colon neoplasm.