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Int. J. Mol. Sci. 2019, 20(5), 1158;

Key Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells

Skin Cancer Centre Charité, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
Department of Dermatology and Venereology, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
Clinic for Dermatology and Venereology, Helios Klinikum Krefeld, Lutherplatz 40, 47805 Krefeld, Germany
Institute of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Leibniz Institute of Catalysis at the University of Rostock e.V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Author to whom correspondence should be addressed.
Received: 8 February 2019 / Revised: 27 February 2019 / Accepted: 2 March 2019 / Published: 7 March 2019
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Cutaneous T-cell lymphoma (CTCL) may develop a highly malignant phenotype in its late phase, and patients may profit from innovative therapies. The plant extract indirubin and its chemical derivatives represent new and promising antitumor strategies. This first report on the effects of an indirubin derivative in CTCL cells shows a strong decrease of cell proliferation and cell viability as well as an induction of apoptosis, suggesting indirubin derivatives for therapy of CTCL. As concerning the mode of activity, the indirubin derivative DKP-071 activated the extrinsic apoptosis cascade via caspase-8 and caspase-3 through downregulation of the caspase antagonistic proteins c-FLIP and XIAP. Importantly, a strong increase of reactive oxygen species (ROS) was observed as an immediate early effect in response to DKP-071 treatment. The use of antioxidative pre-treatment proved the decisive role of ROS, which turned out upstream of all other proapoptotic effects monitored. Thus, reactive oxygen species appear as a highly active proapoptotic pathway in CTCL, which may be promising for therapeutic intervention. This pathway can be efficiently activated by an indirubin derivative. View Full-Text
Keywords: CTCL; apoptosis; cell viability; c-FLIP; XIAP CTCL; apoptosis; cell viability; c-FLIP; XIAP

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Soltan, M.Y.; Sumarni, U.; Assaf, C.; Langer, P.; Reidel, U.; Eberle, J. Key Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells. Int. J. Mol. Sci. 2019, 20, 1158.

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