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 Jul;19(9):1187-9. doi: 10.1096/fj.04-3477fje. Epub 2005 May 3.


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.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Burkitt Lymphoma / chemistry*
  • Burkitt Lymphoma / drug therapy
  • Cell Line, Tumor
  • Clomipramine / pharmacology
  • Fenfluramine / pharmacology
  • Fluoxetine / pharmacology
  • Humans
  • Lymphoma, B-Cell / chemistry*
  • Lymphoma, B-Cell / drug therapy
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Psychotropic Drugs / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins / analysis*
  • Serotonin Plasma Membrane Transport Proteins / drug effects
  • Serotonin Plasma Membrane Transport Proteins / physiology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Psychotropic Drugs
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Fluoxetine
  • Fenfluramine
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Clomipramine