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.
Szegedi
Z
Z
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.
Takács
J
J
Szende
B
B
Vadász
Z
Z
Horváth
A
A
Gulyás
E
E
Tóth
G
G
Peták
I
I
Bocsi
J
J
Kéri
G
G
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