Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-6989
Authors: | Markowitsch, Sascha D. Vakhrusheva, Olesya Schupp, Patricia Akele, Yasminn Kitanovic, Jovana Slade, Kimberly S. Efferth, Thomas Thomas, Anita Tsaur, Igor Mager, René Haferkamp, Axel Jüngel, Eva |
Title: | Shikonin inhibits cell growth of sunitinib-resistant renal cell carcinoma by activating the necrosome complex and inhibiting the AKT/mTOR signaling pathway |
Online publication date: | 20-Dec-2022 |
Year of first publication: | 2022 |
Language: | english |
Abstract: | Therapy resistance remains a major challenge in treating advanced renal cell carcinoma (RCC), making more effective treatment strategies crucial. Shikonin (SHI) from traditional Chinese medicine has exhibited antitumor properties in several tumor entities. We, therefore, currently investigated SHI’s impact on progressive growth and metastatic behavior in therapy-sensitive (parental) and therapy-resistant Caki-1, 786-O, KTCTL-26, and A498 RCC cells. Tumor cell growth, proliferation, clonogenic capacity, cell cycle phase distribution, induction of cell death (apoptosis and necroptosis), and the expression and activity of regulating and signaling proteins were evaluated. Moreover, the adhesion and chemotactic activity of the RCC cells after exposure to SHI were investigated. SHI significantly inhibited the growth, proliferation, and clone formation in parental and sunitinib-resistant RCC cells by G2/M phase arrest through down-regulation of cell cycle activating proteins. Furthermore, SHI induced apoptosis and necroptosis by activating necrosome complex proteins. Concomitantly, SHI impaired the AKT/mTOR pathway. Adhesion and motility were cell line specifically affected by SHI. Thus, SHI may hold promise as an additive option in treating patients with advanced and therapy-resistant RCC. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-6989 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Cancers 14 5 |
Pages or article number: | 1114 |
Publisher: | MDPI |
Publisher place: | Basel |
Issue date: | 2022 |
ISSN: | 2072-6694 |
Publisher URL: | https://doi.org/10.3390/cancers14051114 |
Publisher DOI: | 10.3390/cancers14051114 |
Appears in collections: | DFG-491381577-G |
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![]() | shikonin_inhibits_cell_growth-20220517120048851.pdf | 3.46 MB | Adobe PDF | View/Open |