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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
Version: Published version
Publication type: Zeitschriftenaufsatz
Document type specification: Scientific article
License: CC BY
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Journal: Cancers
Pages or article number: 1114
Publisher: MDPI
Publisher place: Basel
Issue date: 2022
ISSN: 2072-6694
Publisher URL:
Publisher DOI: 10.3390/cancers14051114
Appears in collections:DFG-491381577-G

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