PMID- 15870169
OWN - NLM
STAT- MEDLINE
DCOM- 20060223
LR  - 20220408
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 19
IP  - 9
DP  - 2005 Jul
TI  - The serotonin transporter (SLC6A4) is present in B-cell clones of diverse 
      malignant origin: probing a potential anti-tumor target for psychotropics.
PG  - 1187-9
AB  - 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.
FAU - Meredith, Elizabeth J
AU  - Meredith EJ
AD  - Division of Immunity and Infection, The Medical School, Birmingham, UK.
FAU - Holder, Michelle J
AU  - Holder MJ
FAU - Chamba, Anita
AU  - Chamba A
FAU - Challa, Anita
AU  - Challa A
FAU - Drake-Lee, Adrian
AU  - Drake-Lee A
FAU - Bunce, Christopher M
AU  - Bunce CM
FAU - Drayson, Mark T
AU  - Drayson MT
FAU - Pilkington, Geoffrey
AU  - Pilkington G
FAU - Blakely, Randy D
AU  - Blakely RD
FAU - Dyer, Martin J S
AU  - Dyer MJ
FAU - Barnes, Nicholas M
AU  - Barnes NM
FAU - Gordon, John
AU  - Gordon J
LA  - eng
GR  - DA-07390/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050503
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (SLC6A4 protein, human)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 2DS058H2CF (Fenfluramine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - NUV44L116D (Clomipramine)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Burkitt Lymphoma/*chemistry/drug therapy
MH  - Cell Line, Tumor
MH  - Clomipramine/pharmacology
MH  - Fenfluramine/pharmacology
MH  - Fluoxetine/pharmacology
MH  - Humans
MH  - Lymphoma, B-Cell/*chemistry/drug therapy
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/analysis/physiology
MH  - Psychotropic Drugs/*pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/*analysis/drug effects/physiology
EDAT- 2005/05/05 09:00
MHDA- 2006/02/24 09:00
CRDT- 2005/05/05 09:00
PHST- 2005/05/05 09:00 [pubmed]
PHST- 2006/02/24 09:00 [medline]
PHST- 2005/05/05 09:00 [entrez]
AID - 04-3477fje [pii]
AID - 10.1096/fj.04-3477fje [doi]
PST - ppublish
SO  - FASEB J. 2005 Jul;19(9):1187-9. doi: 10.1096/fj.04-3477fje. Epub 2005 May 3.