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

@article{citeulike:3194453, abstract = {Following 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.}, address = {Division of Immunity and Infection, The Medical School, Birmingham, UK.}, author = {Meredith, E. J. and Holder, M. J. and Chamba, A. and Challa, A. and Drake-Lee, A. and Bunce, C. M. and Drayson, M. T. and Pilkington, G. and Blakely, R. D. and Dyer, M. J. and Barnes, N. M. and Gordon, J.}, citeulike-article-id = {3194453}, citeulike-linkout-0 = {http://dx.doi.org/10.1096/fj.04-3477fje}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15870169}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15870169}, doi = {10.1096/fj.04-3477fje}, issn = {1530-6860}, journal = {The FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, keywords = {b-cell, sert}, month = {July}, number = {9}, pages = {1187--1189}, posted-at = {2008-09-04 17:53:26}, priority = {2}, title = {The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics.}, url = {http://dx.doi.org/10.1096/fj.04-3477fje}, volume = {19}, year = {2005} }

TY - JOUR ID - citeulike:3194453 L3 - citeulike-article-id:3194453 N2 - Following 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. IS - 9 JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology SN - 1530-6860 AD - Division of Immunity and Infection, The Medical School, Birmingham, UK. EP - 1189 TI - The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics. VL - 19 SP - 1187 KW - b-cell KW - sert AU - Meredith, EJ AU - Holder, MJ AU - Chamba, A AU - Challa, A AU - Drake-Lee, A AU - Bunce, CM AU - Drayson, MT AU - Pilkington, G AU - Blakely, RD AU - Dyer, MJ AU - Barnes, NM AU - Gordon, J PY - 2005/07// UR - http://dx.doi.org/10.1096/fj.04-3477fje ER -