The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics

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dc.contributor.authorMeredith, E. J.en
dc.contributor.authorHolder, M. J.en
dc.contributor.authorChamba, A.en
dc.contributor.authorChalla, A.en
dc.contributor.authorDrake-Lee, A.en
dc.contributor.authorBunce, C. M.en
dc.contributor.authorDrayson, M. T.en
dc.contributor.authorPilkington, G.en
dc.contributor.authorBlakely, R. D.en
dc.contributor.authorDyer, M. J.en
dc.contributor.authorBarnes, N. M.en
dc.contributor.authorGordon, J.en
dc.date.accessioned2015-11-24T19:24:44Z
dc.date.available2015-11-24T19:24:44Z
dc.identifier.issn1530-6860-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/22521
dc.rightsDefault Licence-
dc.subjectAntineoplastic Agents/*pharmacologyen
dc.subjectApoptosis/drug effectsen
dc.subjectBurkitt Lymphoma/*chemistry/drug therapyen
dc.subjectCell Line, Tumoren
dc.subjectClomipramine/pharmacologyen
dc.subjectFenfluramine/pharmacologyen
dc.subjectFluoxetine/pharmacologyen
dc.subjectHumansen
dc.subjectLymphoma, B-Cell/*chemistry/drug therapyen
dc.subjectN-Methyl-3,4-methylenedioxyamphetamine/pharmacologyen
dc.subjectP-Glycoprotein/analysisen
dc.subjectProto-Oncogene Proteins c-bcl-2/analysis/physiologyen
dc.subjectPsychotropic Drugs/*pharmacologyen
dc.subjectSerotonin Plasma Membrane Transport Proteins/*analysis/drug effects/physiologyen
dc.titleThe serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropicsen
heal.abstractFollowing our previous description of the serotonin transporter (SERT) acting as a conduit to 5-hydroxytryptamine (5-HT)-mediated apoptosis, specifically in Burkitt's lymphoma, we now detail its expression among a broad spectrum of B cell malignancy, while exploring additional SERT substrates for potential therapeutic activity. SERT was readily detected in derived B cell lines with origins as diverse as B cell precursor acute lymphoblastic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and multiple myeloma. Concentration and timecourse kinetics for the antiproliferative and proapoptotic activities of the amphetamine derivatives fenfluramine (an appetite suppressant) and 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") revealed them as being similar to the endogenous indoleamine. A tricyclic antidepressant, clomipramine, instead mirrored the behavior of the selective serotonin reuptake inhibitor fluoxetine, both being effective in the low micromolar range. A majority of neoplastic clones were sensitive to one or more of the serotonergic compounds. Dysregulated bcl-2 expression, either by t(14;18)(q32;q21) translocation or its introduction as a constitutively active transgene, provided protection from proapoptotic but not antiproliferative outcomes. These data indicate a potential for SERT as a novel anti-tumor target for amphetamine analogs, while evidence is presented that the seemingly more promising antidepressants are likely impacting malignant B cells independently of the transporter itself.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1096/fj.04-3477fje-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/15870169-
heal.identifier.secondaryhttp://www.fasebj.org/content/early/2005/06/29/fj.04-3477fje.full.pdf-
heal.journalNameFaseb Journalen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2005-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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