The apoptotic effect of somatostatin analogue SMS 201-995 on human lymphocytes

Lattuada, D.; Casnici, Claudia; Venuto, Annunziata; Marelli, O

doi:10.1016/s0165-5728(02)00364-8

Cited by 38 publications

(24 citation statements)

References 14 publications

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“…3 Beside its apoptotic action on cancer cells, somatostatin has also been shown to decrease cell survival in several non-cancer cell models, including intestinal epithelial cells, 4 fibroblasts from Graves' ophtalmopathy 6 and peripheral blood lymphocytes. [7][8][9] However, mechanisms for somatostatin-induced apoptosis and receptor subtype implication were not described in these models. Therefore, our results provide the first demonstration of an sst2-mediated apoptotic effect in a noncancer cell model.…”

Section: Discussionmentioning

confidence: 99%

“…2 Whereas somatostatin effect on cell cycle arrest has been extensively studied, mechanisms for somatostatin-induced apoptosis and receptor subtype implication are only partially elucidated. Somatostatin has been shown to induce cell death in both normal and tumoral cell models [3][4][5][6][7][8][9] . Among the five somatostatin receptors, sst3 and sst2 have been found to play a critical role in somatostatin-induced apoptosis of normal and tumor cells, respectively.…”

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confidence: 99%

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Novel synergistic mechanism for sst2 somatostatin and TNFα receptors to induce apoptosis: crosstalk between NF-κB and JNK pathways

et al. 2006

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Somatostatin is a multifunctional hormone that modulates cell proliferation, differentiation and apoptosis. Mechanisms for somatostatin-induced apoptosis are at present mostly unsolved. Therefore, we investigated whether somatostatin receptor subtype 2 (sst2) induces apoptosis in the nontransformed murine fibroblastic NIH3T3 cells. Somatostatin receptor subtype 2 expression induced an executioner caspase-mediated apoptosis through a tyrosine phosphatase SHP-1 (Src homology domain phosphatase-1)-dependent stimulation of nuclear factor kappa B (NF-jB) activity and subsequent inhibition of the mitogenactivated protein kinase JNK. Tumor necrosis factor a (TNFa) stimulated both NF-jB and c-Jun NH2-terminal kinase (JNK) activities, which had opposite action on cell survival. Importantly, sst2 sensitized NIH3T3 cells to TNFa-induced apoptosis by (1) upregulating TNFa receptor protein expression, and sensitizing to TNFa-induced caspase-8 activation; (2) enhancing TNFamediated activation of NF-jB, resulting in JNK inhibition and subsequent executioner caspase activation and cell death. We have here unraveled a novel signaling mechanism for a G protein-coupled receptor, which directly triggers apoptosis and crosstalks with a death receptor to enhance death ligand-induced apoptosis. Somatostatin is a regulatory peptide which is mostly expressed in the central and peripheral nervous system, in the gastro-intestinal tract and in the pancreas. Somatostatin acts via a family of five G protein-coupled receptors (GPCR), somatostatin receptor subtypes 1-5 (sst1-sst5) that are variably expressed throughout numerous tissues ranging from the central nervous system to the endocrine and immune systems. 1 Somatostatin or its analogues promote growth inhibition of various normal and tumor cells, both in vitro and in vivo. Somatostatin affects cell growth indirectly by inhibiting either trophic or growth factor synthesis and/or secretion, or their respective intracellular pathways. Somatostatin antiproliferative action also results from a direct blockade of cell cycle and/or induction of apoptosis. 2 Whereas somatostatin effect on cell cycle arrest has been extensively studied, mechanisms for somatostatin-induced apoptosis and receptor subtype implication are only partially elucidated. Somatostatin has been shown to induce cell death in both normal and tumoral cell models 3-9 . Among the five somatostatin receptors, sst3 and sst2 have been found to play a critical role in somatostatin-induced apoptosis of normal and tumor cells, respectively. 3,5,10 Mechanisms for somatostatin apoptotic action were shown to rely on the mitochondrial pathway through activation either of sst2 or sst3. However, signaling pathways coupling sst2 receptor to apoptosis have been partially elucidated.We have previously demonstrated that expression of sst2 in the nontransformated murine fibroblastic NIH3T3 cells results in a cell growth inhibition, which was dependent on the activation of the tyrosine phosphatase Src homology domain phosphatase-1 (SHP-1). 11 sst2...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Novel synergistic mechanism for sst2 somatostatin and TNFα receptors to induce apoptosis: crosstalk between NF-κB and JNK pathways

et al. 2006

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“…The mechanisms of these antiinflammatory activities of SST are poorly understood, but seem to include both a direct effect of SST on immune cells [37][38][39][40] and an indirect one through glucocorticoids, since SST in macrophages might increase glucocorticoid binding and signaling by stabilizing the glucocorticoid receptor-associated induced heat shock protein Hsp90 [49]. Beside these effects, endogenously produced SST might, in an autocrine or paracrine manner, also affect a number of other immune functions, such as lymphocyte proliferation, immunoglobulin production and cell-mediated activities [37][38][39][40][41][42][43][44][45]. These effects are, however, dependent on the time and dose of SST administration, as well as on the manner of activation of lymphoid cells, implying the involvement of different types of SST receptors and various types of interactions with activated transductional pathways.…”

Section: Discussionmentioning

confidence: 99%

“…These effects include its neurotransmitter functions and increased potency in the inhibition of hormone secretions [29][30][31][32][33][34], but also its participation in antiinflammatory actions of glucocorticoids [35,36] and its marked immunosuppressive, antiproliferative and proapoptotic actions on lymphatic cells [37][38][39][40][41][42][43][44][45].…”

Section: Introductionmentioning

confidence: 99%

Induction of Experimental Allergic Encephalomyelitis in a Low-Susceptible Albino Oxford Rat Strain by Somatostatin Analogue SMS 201-995

Muhvić

Barac-Latas

Rukavina

et al. 2005

Neuroimmunomodulation

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Objective: The effect of the somatostatin analogue SMS 201-995 (octreotide; OCT) on the course of experimental allergic encephalomyelitis (EAE) in the relatively resistant Albino Oxford (AO) strain of rats was studied. Methods: Animals were actively immunized with bovine brain homogenate in complete Freund’s adjuvant. OCT was given subcutaneously in the hind legs on days 7, 8 and 9 after immunization, at a dose of 3 × 5 µg/kg/day. Rats in control groups were treated with saline or were left untreated. EAE was scored clinically and immunophenotypically, estimating by flow cytometry the changes in the popliteal lymph nodes (PLN) and spleen and monitoring immunohistologically the brain sections of rats recovered from disease. Results: In control AO rats, EAE was induced in only 2 of 22 rats (9%). In OCT-treated rats, however, EAE developed in 11 of 20 rats (55%), in comparison with 3 of 17 saline-treated animals (17%) (p < 0.05). In PLN of OCT-treated rats during the clinical course of EAE, a decreased proportion of OX8+ cells was seen, followed by increases in OX39+ and W3/25+ cells on days 17 and 26. In spleen, OCT decreased the proportion of OX1+, OX39+ and OX8+ cells (on days 12 and/or 17), and increased the proportion of OX39+ cells on days 26 and 31. In the brain sections of saline-treated rats recovered from EAE, numerous Mac-1+, Mac-3+ and OX8+ cells were found. These cells were, however, absent in OCT-treated rats; instead, several W3/25+ cells were noticed. Conclusions: These data imply that OCT increases the susceptibility of AO rats to EAE, interfering with specific and/or nonspecific defense mechanisms operating in both the initial and recovery phase of EAE.

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“…Studie in vitro prokazují, že všechny receptorové subtypy (SSTR1-5) se mohou podílet na inhibici buněčné proliferace cestou intracelulár-ních signálních drah, primárně cestou MAP-kináz a aktivací fosfotyrozinfosfatáz [14,15]. Specifické receptorové subtypy (SSTR2, SSTR3) vedou k apoptóze [16]. Nepřímý antiproliferativní účinek zahrnuje inhibici sekrece růsto- Klinické studie potvrzující protinádorový účinek SSA v léčbě neresekabilních/ metastatických NET Antiproliferační efekt oktreotidu LAR byl prokázán v randomizované, placebem kontrolované studii fáze III PROMID, která prokázala prodloužení doby do progrese tumoru (time to progression -TTP) u NET G1 středního střeva (midgut) při léčbě oktreotidem LAR 30 mg ve srovnání s placebem [34].…”

Section: Mechanizmus Vlivu Ssa Na Růst Nádoruunclassified

Antiproliferative Effect of Somatostatin Analogs – Data Analyses and Clinical Applications in the Context of the CLARINET Study

Bencsiková¹

2016

Klin Onkol

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Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno RECAMO, Masarykův onkologický ústav, Brno SouhrnVýchodiska: Somatostatinová analoga (SSA) jsou již více než dvě desetiletí využívána k léčbě hormonálních syndromů spojených s neuroendokrinními nádory. V posledních letech dvě randomizované placebem kontrolované klinické studie fáze III prokazují jejich antiproliferační účinek. Protinádorový účinek oktreotidu LAR (long-acting repeatable) byl prokázán v randomizované, placebem kontrolované studii fáze III PROMID. Antiproliferační efekt lanreotidu autogel byl prokázán v mezinárodní multicentrické placebem kontrolované studii fáze III CLARINET. Lanreotid v léčbě pa cientů s metastatickým gastroenteropankreatickým neuroendokrinním nádorem (GEP-NET) signifikantně prodlužuje dobu přežití bez známek progrese onemocnění. Vzhledem k bio logické odlišnosti GEP-NET může být oddálení progrese onemocnění obtížné, závisí na pů-vodu primárního nádoru a funkčním stavu. Cíl: V souhrnném článku analyzuji data potvrzující roli SSA, se zaměřením na lanreotid, jako antiproliferačních látek v léčbě pa cientů s GEP-NET. Závěr: Studie CLARINET dnes představuje nejsilnější randomizovanou studii zabývající se antiproliferačním efektem SSA u pa cientů s GEP-NET. Medián přežití bez progrese v základní studii CLARI-NET nebo v její open-label extenzi při léčbě lanreotidem byl 32,8 vs. 18 měsíců při léčbě placebem. Včasné zahájení léčby přináší pa cientům benefit v oddálení progrese onemocnění. Nyní je doporučena léčba lanreotidem u pa cientů s dobře diferencovaným metastatickým grade 1 a grade 2 GEP-NET (tedy s Ki-67 proliferačním indexem < 10 %) lokalizovaným v pankreatu, tenkém střevě nebo v případě neznámého prima, nezávisle na rozsahu jaterního postižení. Dostupná data prokazují, že léčba lanreotidem významně prodlužuje čas do progrese u pa cientů s metastatickým GEP-NET. Klíčová slovasomatostatin -neuroendokrinní nádory -angiogeneze -apoptóza -antiproliferační efekt Práce byla podpořena projektem MŠMT-NPU I-LO1413. This work was supported by MEYS-NPS I-LO1413.Autorka deklaruje, že v souvislosti s předmětem studie nemá žádné komerční zájmy.The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study.Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do bi omedicínských časopisů.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. . Představují heterogenní skupinu nádorů vznikající v růz-ných orgánech, zejména v zažívacím traktu, plicích, pankreatu, močovém traktu, v kůži a jinde. Jejich bio logické chování může být zcela indolentní až vysoce agresivní. Rozdíly jsou i v klinických projevech, v závislosti na přítom-nosti hormonální aktivity. Zvláštní skupinu zahrnují gastroenteropankreatické NET (GEP-NET), které se dělí podle WHO klasifikace z roku 2010 (založené na hodnocení stupně diferenciace, gradu, mitotickém indexu, Ki-67) na NET dobře diferencované grade 1 a 2 (NET G1 a G2) ...

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The apoptotic effect of somatostatin analogue SMS 201-995 on human lymphocytes

Cited by 38 publications

References 14 publications

Novel synergistic mechanism for sst2 somatostatin and TNFα receptors to induce apoptosis: crosstalk between NF-κB and JNK pathways

Novel synergistic mechanism for sst2 somatostatin and TNFα receptors to induce apoptosis: crosstalk between NF-κB and JNK pathways

Induction of Experimental Allergic Encephalomyelitis in a Low-Susceptible Albino Oxford Rat Strain by Somatostatin Analogue SMS 201-995

Antiproliferative Effect of Somatostatin Analogs – Data Analyses and Clinical Applications in the Context of the CLARINET Study

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