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The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics.
FASEB J 2005; 19(9):1187-9FJ

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.

Authors+Show Affiliations

Division of Immunity and Infection, The Medical School, Birmingham, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15870169

Citation

Meredith, Elizabeth J., et al. "The Serotonin Transporter (SLC6A4) Is Present in B-cell Clones of Diverse Malignant Origin: Probing a Potential Anti-tumor Target for Psychotropics." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 19, no. 9, 2005, pp. 1187-9.
Meredith EJ, Holder MJ, Chamba A, et al. The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics. FASEB J. 2005;19(9):1187-9.
Meredith, E. J., Holder, M. J., Chamba, A., Challa, A., Drake-Lee, A., Bunce, C. M., ... Gordon, J. (2005). The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 19(9), pp. 1187-9.
Meredith EJ, et al. The Serotonin Transporter (SLC6A4) Is Present in B-cell Clones of Diverse Malignant Origin: Probing a Potential Anti-tumor Target for Psychotropics. FASEB J. 2005;19(9):1187-9. PubMed PMID: 15870169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics. AU - Meredith,Elizabeth J, AU - Holder,Michelle J, AU - Chamba,Anita, AU - Challa,Anita, AU - Drake-Lee,Adrian, AU - Bunce,Christopher M, AU - Drayson,Mark T, AU - Pilkington,Geoffrey, AU - Blakely,Randy D, AU - Dyer,Martin J S, AU - Barnes,Nicholas M, AU - Gordon,John, Y1 - 2005/05/03/ PY - 2005/5/5/pubmed PY - 2006/2/24/medline PY - 2005/5/5/entrez SP - 1187 EP - 9 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 19 IS - 9 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. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/15870169/The_serotonin_transporter__SLC6A4__is_present_in_B_cell_clones_of_diverse_malignant_origin:_probing_a_potential_anti_tumor_target_for_psychotropics_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.04-3477fje?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -