Growth inhibitory effect of the somatostatin structural derivative (TT-232) on leukemia models.

Abstract

TT-232 is a structural derivative of the natural signal inhibitory peptide somatostatin, with selective antiproliferative and anti-inflammatory properties. TT-232 activates SSTR receptors (primarily the SSTR-1), which leads to irreversible cell cycle arrest, followed by secondary induction of apoptosis. TT-232 has passed phase I clinical trials without toxicity and significant side-effects. We examined the antiproliferative effect in vitro and the antitumor effect in vivo of TT-232 on leukemia cell lines. During in vivo experiments, we evaluated the therapeutic efficacy of TT-232 in various long-term administration routes; traditional injection versus infusion treatment via an inserted Alzet minipump on P-388 mice and HL-60 human leukemia models. Treatment with TT-232 started after development of the disease. In vitro, TT-232 inhibited the proliferation of P-388 mice lymphoid cells and HL-60 human promyelocytic leukemia cells in the range of 46%-97% with 24-hour treatment and 82%-100% with 48-hour treatment. Cells were treated with 30 microg/ml and 60 microg/ml dose of TT-232. With the same in vivo models, the best results were achieved when TT-232 was applied by infusion treatments. The infusion treatment with TT-232 produced 50%-80% inhibition of growth and resulted in 20%-40% long-term and leukemia-free survivors. TT-232 showed dose-, time- and administration mode-dependent antileukemia activity in vitro and in vivo, both on rodent and human models. Our results suggest that TT-232 is a promising new antileukemia agent.

• Authors: M Tejeda, D Gaál, O Csuka, Gy Kéri
• Journal: Anticancer research (Anticancer Res) 2005 Jan-Feb Vol. 25 Issue 1A Pg. 325-30 ISSN: 0250-7005 [Print] Greece
• PMID: 15816555 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Growth Inhibitors
• Peptides, Cyclic
• TT2-32
• Somatostatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Female
• Growth Inhibitors (pharmacology)
• HL-60 Cells
• Humans
• Leukemia P388 (drug therapy)
• Leukemia, Promyelocytic, Acute (drug therapy)
• Mice
• Mice, Inbred CBA
• Peptides, Cyclic (pharmacology)
• Somatostatin (analogs & derivatives)