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

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Published on Friday, 13 December 2013

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.

 

 

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