The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics
Φόρτωση...
Ημερομηνία
Συγγραφείς
Meredith, E. J.
Holder, M. J.
Chamba, A.
Challa, A.
Drake-Lee, A.
Bunce, C. M.
Drayson, M. T.
Pilkington, G.
Blakely, R. D.
Dyer, M. J.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Faseb Journal
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
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.
Περιγραφή
Λέξεις-κλειδιά
Antineoplastic Agents/*pharmacology, Apoptosis/drug effects, Burkitt Lymphoma/*chemistry/drug therapy, Cell Line, Tumor, Clomipramine/pharmacology, Fenfluramine/pharmacology, Fluoxetine/pharmacology, Humans, Lymphoma, B-Cell/*chemistry/drug therapy, N-Methyl-3,4-methylenedioxyamphetamine/pharmacology, P-Glycoprotein/analysis, Proto-Oncogene Proteins c-bcl-2/analysis/physiology, Psychotropic Drugs/*pharmacology, Serotonin Plasma Membrane Transport Proteins/*analysis/drug effects/physiology
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/15870169
http://www.fasebj.org/content/early/2005/06/29/fj.04-3477fje.full.pdf
http://www.fasebj.org/content/early/2005/06/29/fj.04-3477fje.full.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής