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Volume 20
Issue 5
10.3390/ijms20051158
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Article

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

by
Marwa Y. Soltan
1,2,
Uly Sumarni
1,
Chalid Assaf
1,3,
Peter Langer
4,5,
Ulrich Reidel
1 and
Jürgen Eberle
1,*
1
Skin Cancer Centre Charité, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
2
Department of Dermatology and Venereology, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
3
Clinic for Dermatology and Venereology, Helios Klinikum Krefeld, Lutherplatz 40, 47805 Krefeld, Germany
4
Institute of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
5
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.
Int. J. Mol. Sci. 2019, 20(5), 1158; https://doi.org/10.3390/ijms20051158
Received: 8 February 2019 / Revised: 27 February 2019 / Accepted: 2 March 2019 / Published: 7 March 2019
(This article belongs to the Special Issue Physiological and Pathological Role of ROS: Benefits and Limitations of Antioxidant Treatment)
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Abstract

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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MDPI and ACS Style

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. https://doi.org/10.3390/ijms20051158

AMA Style

Soltan MY, 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. International Journal of Molecular Sciences. 2019; 20(5):1158. https://doi.org/10.3390/ijms20051158

Chicago/Turabian Style

Soltan, Marwa Y., Uly Sumarni, Chalid Assaf, Peter Langer, Ulrich Reidel, and Jürgen Eberle. 2019. "Key Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells" International Journal of Molecular Sciences 20, no. 5: 1158. https://doi.org/10.3390/ijms20051158

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