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Psoralen with ultraviolet A‐induced apoptosis of cutaneous lymphoma cell lines is augmented by type I interferons via the JAK1–STAT1 pathway
Author(s) -
Liszewski Walter,
Naym David Gram,
Biskup Edyta,
Gniadecki Robert
Publication year - 2017
Publication title -
photodermatology, photoimmunology and photomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.736
H-Index - 60
eISSN - 1600-0781
pISSN - 0905-4383
DOI - 10.1111/phpp.12302
Subject(s) - mycosis fungoides , psoralen , puva therapy , apoptosis , cancer research , cell culture , cutaneous t cell lymphoma , interferon , lymphoma , biology , chemistry , immunology , psoriasis , dna , biochemistry , genetics
Summary Background Photochemotherapy with psoralen and ultraviolet A (PUVA), with or without adjuvant interferon‐α (IFN‐α), is a first‐line therapy for early‐stage mycosis fungoides and other forms of cutaneous T‐cell lymphoma (CTCL). However, the mechanism by which PUVA with IFN‐α work in CTCL is poorly understood. Purpose To develop a model to investigate the mechanisms of PUVA and PUVA with IFN‐α in CTCL cells. Methods An in vitro model to study the molecular mechanisms of PUVA was created using two different CTCL cell lines, MyLa, which has functional p53, and HuT‐78, in which p53 is inactivated due to a homozygous nonsense mutation. Results PUVA caused G2/M cell cycle block and apoptosis of MyLa and HuT‐78 accompanied by increase in the expression of the mitochondrial pro‐apoptotic genes Bax, BAK, and PUMA and a downregulation in anti‐apoptotic Bcl‐2. p53 was induced and c‐Myc was repressed by PUVA, but neither were essential for PUVA‐induced apoptosis. IFN‐α augmented PUVA‐induced apoptosis via the JAK1 pathway, and this activity could be inhibited by ruxolitinib. Conclusion PUVA induces p53‐independent apoptosis in CTCL cell lines, and this process is augmented by type I interferons via the JAK1 pathway.