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Article

A Thia-Analogous Indirubin N-Glycoside Disrupts Mitochondrial Function and Causes the Death of Human Melanoma and Cutaneous Squamous Cell Carcinoma Cells

by
Franziska Wendt
1,
Felix Wittig
1,
Anne Rupprecht
1,
Robert Ramer
1,
Peter Langer
2,
Steffen Emmert
3,
Marcus Frank
4,5 and
Burkhard Hinz
1,*
1
Institute of Pharmacology and Toxicology, Rostock University Medical Centre, 18057 Rostock, Germany
2
Institute of Organic Chemistry, University of Rostock, 18059 Rostock, Germany
3
Clinic and Policlinic for Dermatology, Rostock University Medical Centre, 18057 Rostock, Germany
4
Electron Microscopy Centre, Rostock University Medical Centre, 18057 Rostock, Germany
5
Department Life, Light and Matter, University of Rostock, 18059 Rostock, Germany
*
Author to whom correspondence should be addressed.
Cells 2023, 12(19), 2409; https://doi.org/10.3390/cells12192409
Submission received: 10 March 2023 / Revised: 8 September 2023 / Accepted: 20 September 2023 / Published: 5 October 2023
(This article belongs to the Special Issue Skin Research: Cellular Mechanism and Therapeutic Potentials)
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Abstract

Skin cancer is the most common malignant disease worldwide and, therefore, also poses a challenge from a pharmacotherapeutic perspective. Derivatives of indirubin are an interesting option in this context. In the present study, the effects of 3-[3′-oxo-benzo[b]thiophen-2′-(Z)-ylidene]-1-(β-d-glucopyranosyl)-oxindole (KD87), a thia-analogous indirubin N-glycoside, on the viability and mitochondrial properties of melanoma (A375) and squamous cell carcinoma cells (A431) of the skin were investigated. In both cell lines, KD87 caused decreased viability, the activation of caspases-3 and -7, and the inhibition of colony formation. At the mitochondrial level, a concentration-dependent decrease in both the basal and ATP-linked oxygen consumption rate and in the reserve capacity of oxidative respiration were registered in the presence of KD87. These changes were accompanied by morphological alterations in the mitochondria, a release of mitochondrial cytochrome c into the cytosol and significant reductions in succinate dehydrogenase complex subunit B (SDHB, subunit of complex II) in A375 and A431 cells and NADH:ubiquinone oxidoreductase subunit B8 (NDUFB8, subunit of complex I) in A375 cells. The effect of KD87 was accompanied by a significant upregulation of the enzyme heme oxygenase-1, whose inhibition led to a partial but significant reduction in the metabolic-activity-reducing effect of KD87. In summary, our data show a mitochondria-targeting effect of KD87 as part of the cytotoxic effect of this compound on skin cancer cells, which should be considered in future studies with this class of compounds.
Keywords: thia-analogous indirubin N-glycoside; skin cancer; melanoma cells; squamous cell carcinoma cells; heme oxygenase-1; mitochondria; oxygen consumption rate; respiratory chain complex proteins thia-analogous indirubin N-glycoside; skin cancer; melanoma cells; squamous cell carcinoma cells; heme oxygenase-1; mitochondria; oxygen consumption rate; respiratory chain complex proteins

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MDPI and ACS Style

Wendt, F.; Wittig, F.; Rupprecht, A.; Ramer, R.; Langer, P.; Emmert, S.; Frank, M.; Hinz, B. A Thia-Analogous Indirubin N-Glycoside Disrupts Mitochondrial Function and Causes the Death of Human Melanoma and Cutaneous Squamous Cell Carcinoma Cells. Cells 2023, 12, 2409. https://doi.org/10.3390/cells12192409

AMA Style

Wendt F, Wittig F, Rupprecht A, Ramer R, Langer P, Emmert S, Frank M, Hinz B. A Thia-Analogous Indirubin N-Glycoside Disrupts Mitochondrial Function and Causes the Death of Human Melanoma and Cutaneous Squamous Cell Carcinoma Cells. Cells. 2023; 12(19):2409. https://doi.org/10.3390/cells12192409

Chicago/Turabian Style

Wendt, Franziska, Felix Wittig, Anne Rupprecht, Robert Ramer, Peter Langer, Steffen Emmert, Marcus Frank, and Burkhard Hinz. 2023. "A Thia-Analogous Indirubin N-Glycoside Disrupts Mitochondrial Function and Causes the Death of Human Melanoma and Cutaneous Squamous Cell Carcinoma Cells" Cells 12, no. 19: 2409. https://doi.org/10.3390/cells12192409

APA Style

Wendt, F., Wittig, F., Rupprecht, A., Ramer, R., Langer, P., Emmert, S., Frank, M., & Hinz, B. (2023). A Thia-Analogous Indirubin N-Glycoside Disrupts Mitochondrial Function and Causes the Death of Human Melanoma and Cutaneous Squamous Cell Carcinoma Cells. Cells, 12(19), 2409. https://doi.org/10.3390/cells12192409

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