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The antihistamines clemastine and desloratadine inhibit STAT 3 and c‐Myc activities and induce apoptosis in cutaneous T‐cell lymphoma cell lines
Author(s) -
Döbbeling Udo,
WaeckerleMen Ying,
Zabel Franziska,
Graf Nicole,
Kündig Thomas M.,
Johansen Pål
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12086
Subject(s) - mycosis fungoides , cancer research , apoptosis , programmed cell death , lymphoma , medicine , cutaneous t cell lymphoma , immunology , t cell , biology , immune system , biochemistry
Mycosis fungoides and its leukaemic counterpart Sézary syndrome are the most frequent cutaneous T‐cell lymphomas ( CTCL ), and there is no cure for these diseases. We evaluated the effect of clinically approved antihistamines on the growth of CTCL cell lines. CTCL cell lines as well as blood lymphocytes from patients with Sézary syndrome were cultured with antihistamines, and the cell were analysed for proliferation, apoptosis and expression of programmed death molecules and transcription factors. The two antihistamines clemastine and desloratadine, currently used for symptom alleviation in allergy, induced potent reduction of the activities of the constitutively active transcription factors c‐Myc, STAT 3, STAT 5a and STAT 5b in mycosis fungoides and Sézary syndrome cell lines. This inhibition was followed by apoptosis and cell death, especially in the Sézary syndrome‐derived cell line Hut78 that also showed increased expression of the programmed death‐1 ( PD ‐1) after clemastine treatment. In lymphocytes isolated from Sézary syndrome patients, the CD 4‐positive fraction underwent apoptosis after clemastine treatment, while CD 4‐negative lymphocytes were little affected. Because both c‐Myc and STAT transcription factors are highly expressed in proliferating tumours, their inhibition by clemastine, desloratadine and other inhibitors could complement established chemotherapies not only for cutaneous T‐cell lymphomas but perhaps also other cancers.