A specifically radiolabeled somatostatin analog with strong antitumor activity induces apoptosis and accumulates in the cytosol and the nucleus of HT29 human colon carcinoma cells

The new heptapeptide somatostatin analog TT-232 decreases proliferation of MT-29 human colon carcinoma cells in vitro by reducing mitotic and increasi ng apoptotic activity. We have synthesized and characterized a specifically tritium labeled H-3-Tyr3-TT-232 (30 Ci/mmol) to investigate the effect and the fate of this antitumor peptide on human colon tumor cells. H-3-labeled TT-232 could be detected on the cell surface, on cytoplasmic membranes and also in the nucleus of MT-29 cells, 1-6 h after the administration of 0.5 and 50 mu g/mL [H-3]TT-232. Binding and internalization of TT-232 to human colon tumor cells at a relatively high dose provide further evidence for th e existence of low-affinity somatostatin receptors in such cells, which mig ht mediate the apoptosis-inducing effect. Our data suggest the possible use of TT-232 in the treatment of human colon tumors.