Psoralen with ultraviolet A-induced apoptosis of cutaneous lymphoma cell lines is augmented by type I interferons via the JAK1-STAT1 pathway

Autor: David Gram Naym, Edyta Biskup, Robert Gniadecki, Walter Joseph Liszewski
Rok vydání: 2017
Předmět:
0301 basic medicine
Gene Expression
Apoptosis
Cutaneous lymphoma
chemistry.chemical_compound
0302 clinical medicine
Interferon
hemic and lymphatic diseases
Immunology and Allergy
STAT1
Psoralen
bcl-2-Associated X Protein
biology
General Medicine
Lymphoma
T-Cell
Cutaneous
G2 Phase Cell Cycle Checkpoints
STAT1 Transcription Factor
bcl-2 Homologous Antagonist-Killer Protein
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
medicine.drug
Signal Transduction
Immunology
Antineoplastic Agents
Dermatology
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
Proto-Oncogene Proteins
Nitriles
medicine
Humans
Janus Kinase Inhibitors
Radiology
Nuclear Medicine and imaging
PUVA Therapy
Mycosis fungoides
Interferon-alpha
Janus Kinase 1
medicine.disease
Lymphoma
030104 developmental biology
Pyrimidines
chemistry
Cancer research
biology.protein
M Phase Cell Cycle Checkpoints
Pyrazoles
Tumor Suppressor Protein p53
Apoptosis Regulatory Proteins
Zdroj: Photodermatology, photoimmunologyphotomedicine. 33(3)
ISSN: 1600-0781
Popis: 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.
Databáze: OpenAIRE
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