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 HT-29 human colon carcinoma cells in vitro by reducing mitotic and increasing apoptotic activity. We have synthesized and characterized a specifically tritium labeled 3H-Tyr3-TT-232 (30 Ci/mmol) to investigate the effect and the fate of this antitumor peptide on human colon tumor cells. 3H-labeled TT-232 could be detected on the cell surface, on cytoplasmic membranes and also in the nucleus of HT-29 cells, 1-6 h after the administration of 0.5 and 50 microg/mL [3H]TT-232. Binding and internalization of TT-232 to human colon tumor cells at a relatively high dose provide further evidence for the existence of low-affinity somatostatin receptors in such cells, which might mediate the apoptosis-inducing effect. Our data suggest the possible use of TT-232 in the treatment of human colon tumors.
1st Institute of Pathology and Experimental Cancer Research, Molecular Pathology Research Unit, Joint Research Organization of the Hungarian Academy of Sciences and Semmelweis University of Medicine, Budapest.
Z
Z
Szegedi
J
J
Takács
B
B
Szende
Z
Z
Vadász
A
A
Horváth
E
E
Gulyás
G
G
Tóth
I
I
Peták
J
J
Bocsi
G
G
Kéri
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D053938:DNA Fragmentation; D005434:Flow Cytometry; D019073:HT29 Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007553:Isotope Labeling; D007700:Kinetics; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D013004:Somatostatin / Q000031:analogs & derivatives; D014316:Tritium
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D014316:Tritium; C094462:TT2-32; D013004:Somatostatin