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SHR Neuro Cancer Cardio Lipid Metab Microb

Kretschmer, N; Deutsch, A; Durchschein, C; Rinner, B; Stallinger, A; Higareda-Almaraz, JC; Scheideler, M; Lohberger, B; Bauer, R.
Comparative Gene Expression Analysis in WM164 Melanoma Cells Revealed That β-β-Dimethylacrylshikonin Leads to ROS Generation, Loss of Mitochondrial Membrane Potential, and Autophagy Induction.
Molecules. 2018; 23(11): Doi: 10.3390/molecules23112823 [OPEN ACCESS]
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Leading authors Med Uni Graz: Kretschmer Nadine
Co-authors Med Uni Graz: Deutsch Alexander; Lohberger Birgit; Rinner Beate; Stallinger Alexander
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Abstract:: Skin cancer is currently diagnosed as one in every three cancers. Melanoma, the most aggressive form of skin cancer, is responsible for 79% of skin cancer deaths and the incidence is rising faster than in any other solid tumor type. Previously, we have demonstrated that dimethylacrylshikonin (DMAS), isolated from the roots of Onosma paniculata (Boraginaceae), exhibited the lowest IC₅₀ values against different tumor types out of several isolated shikonin derivatives. DMAS was especially cytotoxic towards melanoma cells and led to apoptosis and cell cycle arrest. In this study, we performed a comprehensive gene expression study to investigate the mechanism of action in more detail. Gene expression signature was compared to vehicle-treated WM164 control cells after 24 h of DMAS treatment; where 1192 distinct mRNAs could be identified as expressed in all replicates and 89 were at least 2-fold differentially expressed. DMAS favored catabolic processes and led in particular to p62 increase which is involved in cell growth, survival, and autophagy. More in-depth experiments revealed that DMAS led to autophagy, ROS generation, and loss of mitochondrial membrane potential in different melanoma cells. It has been reported that the induction of an autophagic cell death represents a highly effective approach in melanoma therapy.
Find related publications in this database (using NLM MeSH Indexing): Apoptosis - drug effects; Cell Line, Tumor -; Cell Proliferation - drug effects; Gene Expression Regulation - drug effects; Humans -; Melanoma - drug therapy; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects
Find related publications in this database (Keywords): beta-beta-dimethylacrylshikonin; melanoma; p62; autophagy; ROS generation; mitochondrial membrane potential