Shikonin Inhibits Cell Growth of Sunitinib-Resistant Renal Cell Carcinoma by Activating the Necrosome Complex and Inhibiting the AKT/mTOR Signaling Pathway
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Sascha D Markowitsch
- Olesya Vakhrusheva
- Patricia Schupp
- Yasminn Akele
- Jovana Kitanovic
- Kimberly S Slade
- Thomas Efferth
- Anita Thomas
- Igor Tsaur
- Rene Mager
- Axel Haferkamp
- Eva Juengel
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000768087400001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/cancers14051114
- eISSN
- 2072-6694
- Externe Identifier
- Clarivate Analytics Document Solution ID: ZR9HU
- PubMed Identifier: 35267423
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- CANCERS
- Schlüsselwörter
- renal cell carcinoma (RCC)
- sunitinib
- therapy resistance
- shikonin (SHI)
- growth
- necroptosis
- AKT
- Artikelnummer
- ARTN 1114
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Shikonin Inhibits Cell Growth of Sunitinib-Resistant Renal Cell Carcinoma by Activating the Necrosome Complex and Inhibiting the AKT/mTOR Signaling Pathway
- Sub types
- Article
- Ausgabe der Zeitschrift
- 14
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>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.</jats:p>
- Autoren
- Sascha D Markowitsch
- Olesya Vakhrusheva
- Patricia Schupp
- Yasminn Akele
- Jovana Kitanovic
- Kimberly S Slade
- Thomas Efferth
- Anita Thomas
- Igor Tsaur
- René Mager
- Axel Haferkamp
- Eva Juengel
- DOI
- 10.3390/cancers14051114
- eISSN
- 2072-6694
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- Cancers
- Sprache
- en
- Online publication date
- 2022
- Paginierung
- 1114 - 1114
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/cancers14051114
- Datum der Datenerfassung
- 2022
- Titel
- Shikonin Inhibits Cell Growth of Sunitinib-Resistant Renal Cell Carcinoma by Activating the Necrosome Complex and Inhibiting the AKT/mTOR Signaling Pathway
- Ausgabe der Zeitschrift
- 14
Data source: Crossref
- 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.
- Addresses
- Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
- Autoren
- Sascha D Markowitsch
- Olesya Vakhrusheva
- Patricia Schupp
- Yasminn Akele
- Jovana Kitanovic
- Kimberly S Slade
- Thomas Efferth
- Anita Thomas
- Igor Tsaur
- René Mager
- Axel Haferkamp
- Eva Juengel
- DOI
- 10.3390/cancers14051114
- eISSN
- 2072-6694
- Externe Identifier
- PubMed Identifier: 35267423
- PubMed Central ID: PMC8909272
- Funding acknowledgements
- Prof. Dr. Karl und Gerhard Schiller-Stiftung: 10-2017
- Friedrich-Spicker-Stiftung: 10-2017
- Friedrich-Spicker-Stiftung: 01-2016
- Open access
- true
- ISSN
- 2072-6694
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- Cancers
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2022
- Open access status
- Open Access
- Paginierung
- 1114
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2022
- Titel
- Shikonin Inhibits Cell Growth of Sunitinib-Resistant Renal Cell Carcinoma by Activating the Necrosome Complex and Inhibiting the AKT/mTOR Signaling Pathway.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 14
Files
https://www.mdpi.com/2072-6694/14/5/1114/pdf?version=1645676266 https://europepmc.org/articles/PMC8909272?pdf=render
Data source: Europe PubMed Central
- 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.
- Date of acceptance
- 2022
- Autoren
- Sascha D Markowitsch
- Olesya Vakhrusheva
- Patricia Schupp
- Yasminn Akele
- Jovana Kitanovic
- Kimberly S Slade
- Thomas Efferth
- Anita Thomas
- Igor Tsaur
- René Mager
- Axel Haferkamp
- Eva Juengel
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35267423
- DOI
- 10.3390/cancers14051114
- Externe Identifier
- PubMed Central ID: PMC8909272
- Funding acknowledgements
- Friedrich-Spicker-Stiftung: 01-2016
- Prof. Dr. Karl und Gerhard Schiller-Stiftung: 10-2017
- ISSN
- 2072-6694
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- Cancers (Basel)
- Schlüsselwörter
- AKT
- growth
- necroptosis
- renal cell carcinoma (RCC)
- shikonin (SHI)
- sunitinib
- therapy resistance
- Sprache
- eng
- Country
- Switzerland
- PII
- cancers14051114
- Datum der Veröffentlichung
- 2022
- Status
- Published online
- Titel
- Shikonin Inhibits Cell Growth of Sunitinib-Resistant Renal Cell Carcinoma by Activating the Necrosome Complex and Inhibiting the AKT/mTOR Signaling Pathway.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 14
Data source: PubMed
- Author's licence
- CC-BY
- Autoren
- Sascha D Markowitsch
- Olesya Vakhrusheva
- Patricia Schupp
- Yasminn Akele
- Jovana Kitanovic
- Kimberly S Slade
- Thomas Efferth
- Anita Thomas
- Igor Tsaur
- René Mager
- Axel Haferkamp
- Eva Jüngel
- Hosting institution
- Universitätsbibliothek Mainz
- Sammlungen
- DFG-491381577-G
- Resource version
- Published version
- DOI
- 10.3390/cancers14051114
- Funding acknowledgements
- Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577
- File(s) embargoed
- false
- Open access
- true
- ISSN
- 2072-6694
- Ausgabe der Veröffentlichung
- 5
- Zeitschrift
- Cancers
- Schlüsselwörter
- 610 Medizin
- 610 Medical sciences
- Sprache
- eng
- Open access status
- Open Access
- Paginierung
- 1114
- Datum der Veröffentlichung
- 2022
- Public URL
- https://openscience.ub.uni-mainz.de/handle/20.500.12030/7001
- Herausgeber
- MDPI
- Herausgeber URL
- https://doi.org/10.3390/cancers14051114
- Datum der Datenerfassung
- 2022
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Zugang
- Public
- Titel
- Shikonin inhibits cell growth of sunitinib-resistant renal cell carcinoma by activating the necrosome complex and inhibiting the AKT/mTOR signaling pathway
- Ausgabe der Zeitschrift
- 14
Files
shikonin_inhibits_cell_growth-20220517120048851.pdf
Data source: OPENSCIENCE.UB
- Beziehungen:
-