Disease relevance of TT-232

• TT-232 inhibited the growth of HT-18 melanoma xenografts, a dose of 5 mg kg(-1) being the most effective [1].
• Nearly 50% growth inhibition of HT-58 lymphoma was achieved by daily treatment with 1 mg kg(-1) TT-232 [1].
• Apoptosis is induced in both drug-sensitive and multidrug-resistant hepatoma cells by somatostatin analogue TT-232 [2].
• We examined whether TT-232 had antiproliferative activity in human pancreatic cancer cell lines, and compared its antiproliferative activity with that of RC-160 and other TT-232 derivatives [3].
• Antimetastatic effect of TT-232 treatment combined with DTIC was studied using the B16 mouse melanoma muscle - lung metastasis model [1].

High impact information on TT-232

• The SOM receptor antagonist cyclosomatostatin (c-SOM; 20 microg/kg) or, in another group, the synthetic heptapeptide agonist TT-232 (2 x 50-400 microg/kg) was administered intraperitoneally every day [4].
• Lipoamino acid and liposaccharide conjugates of somatostatin analogue TT-232 were synthesized to modify the physicochemical properties of the parent peptide [5].
• A novel somatostatin analogue, TT-232 (which inhibits the proliferation of various cell cultures and transplantable mouse tumours), was examined regarding its effect on human melanoma and lymphoma xenografts as a single treatment or in combination with DTIC (dacarbazine) and etoposide [1].
• TT-232 inhibited the growth of all of the cell lines used in this study and induced apoptotic cell death [3].
• We found a significant PTPase stimulation after TT-232 administration using an immunoblot analysis assessing the level of protein tyrosine phosphorylation, and also a direct measurement of the PTPase activity [3].

Biological context of TT-232

• The somatostatin analogue TT-232 induces apoptosis in A431 cells: sustained activation of stress-activated kinases and inhibition of signalling to extracellular signal-regulated kinases [6].
• At the commitment time for inducing cell death, TT-232 decreased EGFR-tyrosine phosphorylation and prevented epidermial growth factor (EGF)-induced events like cRaf-1 and ERK2 activation [6].
• We found that pulse treatment with TT-232 blocks the cell cycle G(1)/S transition irreversibly in A431 cells [7].
• The somatostatin analogue peptide TT-232 induces apoptosis and chromosome breakage in cultured human lymphocytes [8].
• The somatostatin analogue, TT-232 inhibits cell proliferation and induces apoptosis in a variety of tumor cells both in vivo and in vitro [9].

Anatomical context of TT-232

• TT-232 (up to 5 mg/kg i.p.) did not induce mucosal lesions in either the stomach or the duodenum.These data suggest that TT-232, a somatostatin analogue devoid of endocrine effects, is a promising lead molecule in the search for novel, broad-spectrum anti-inflammatory and analgesic agents [10].
• In accordance, in vitro binding experiments indicated high-affinity binding of TT-232 to (125)I labelled somatostatin sites in brain membranes [11].
• Cutaneous neutrophil accumulation over a 3-h period after intradermal (i.d.) injection of carrageenin (1 mg/site) or interleukin 1beta (IL-1beta, 3 pmol/site) was inhibited significantly by TT-232 (3x80 microg/kg i.v.), while diclofenac (3x10 mg/kg i.v.) elicited significant inhibition only in the IL-1beta test [10].
• TT-232 has no growth hormone release inhibitory effect and does not inhibit the secretion of gastric acid [12].
• 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 [13].

Associations of TT-232 with other chemical compounds

• 2. Cyclic synthetic octapeptide (TT-248 and TT-250) and heptapeptide (TT-232) somatostatin analogues proved to be more effective in reducing neurogenic and non-neurogenic inflammatory reactions but octreotide had no influence on either neurogenic or non-neurogenic inflammation [14].
• The anti-inflammatory action of TT-232 is mediated through the SSTR4 receptor, and its antitumor activity is mediated through the SSTR1 receptor and by the tumor-specific isoform of pyruvate kinase [15].
• In order to study the structure-activity relationships of TT-232, we designed and synthesized an analog of TT-232, namely Lan-7, in which the disulfide bridge is replaced by a lanthionine monosulfide bridge [16].

Gene context of TT-232

• Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232 [9].
• Blocking the signalling to ERK or p38MAPK activation had no effect on the TT-232-induced cell killing [6].
• Our data suggest that TT-232 triggers an apoptotic type of cell death, concomitant with a strong activation of JNK and a blockade of cellular ERK2 activation pathways [6].
• The antitumor somatostatin analogue TT-232 induces cell cycle arrest through PKCdelta and c-Src [7].
• Pharmacological characterisation of the somatostatin analogue TT-232: effects on neurogenic and non-neurogenic inflammation and neuropathic hyperalgesia [10].

Analytical, diagnostic and therapeutic context of TT-232

• TT-232 also inhibited tumour formation in a xenograft model [3].
• These experimental data suggest that TT-232 may be an effective new tool in the combination chemotherapy of malignant tumours like melanoma and lymphoma [1].
• The tumor growth inhibitory effect of TT-232 on human tumor xenografts proved to be significant, resulting in 30%-80% decrease in tumor volume and in 20%-40% tumor-free animals [17].
• TT-232 had previously been shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of different tumors in animal models in vivo [17].
• TT-232 has passed phase I clinical trials without toxicity and significant side-effects [18].

References