Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Sascha D Markowitsch
- Patricia Schupp
- Julia Lauckner
- Olesya Vakhrusheva
- Kimberly S Slade
- Rene Mager
- Thomas Efferth
- Axel Haferkamp
- Eva Juengel
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000593601800001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/cancers12113150
- eISSN
- 2072-6694
- Externe Identifier
- Clarivate Analytics Document Solution ID: OX5JW
- PubMed Identifier: 33121039
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- CANCERS
- Schlüsselwörter
- renal cell carcinoma (RCC)
- sunitib resistance
- artesunate (ART)
- Traditional Chinese Medicine (TCM)
- growth inhibition
- ferroptosis
- reactive oxygen species (ROS)
- Artikelnummer
- ARTN 3150
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis
- Sub types
- Article
- Ausgabe der Zeitschrift
- 12
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to investigate the impact of ART (1–100 µM) on the sunitinib-resistant RCC cell lines, Caki-1, 786-O, KTCTL26, and A-498. Therapy-sensitive (parental) and untreated cells served as controls. ART’s impact on tumor cell growth, proliferation, clonogenic growth, apoptosis, necrosis, ferroptosis, and metabolic activity was evaluated. Cell cycle distribution, the expression of cell cycle regulating proteins, p53, and the occurrence of reactive oxygen species (ROS) were investigated. ART significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant RCC cells. In Caki-1, 786-O, and A-498 cell lines growth inhibition was associated with G0/G1 phase arrest and distinct modulation of cell cycle regulating proteins. KTCTL-26 cells were mainly affected by ART through ROS generation, ferroptosis, and decreased metabolism. p53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.</jats:p>
- Autoren
- Sascha D Markowitsch
- Patricia Schupp
- Julia Lauckner
- Olesya Vakhrusheva
- Kimberly S Slade
- René Mager
- Thomas Efferth
- Axel Haferkamp
- Eva Juengel
- DOI
- 10.3390/cancers12113150
- eISSN
- 2072-6694
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Cancers
- Sprache
- en
- Online publication date
- 2020
- Paginierung
- 3150 - 3150
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/cancers12113150
- Datum der Datenerfassung
- 2020
- Titel
- Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis
- Ausgabe der Zeitschrift
- 12
Data source: Crossref
- Abstract
- Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to investigate the impact of ART (1-100 µM) on the sunitinib-resistant RCC cell lines, Caki-1, 786-O, KTCTL26, and A-498. Therapy-sensitive (parental) and untreated cells served as controls. ART's impact on tumor cell growth, proliferation, clonogenic growth, apoptosis, necrosis, ferroptosis, and metabolic activity was evaluated. Cell cycle distribution, the expression of cell cycle regulating proteins, p53, and the occurrence of reactive oxygen species (ROS) were investigated. ART significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant RCC cells. In Caki-1, 786-O, and A-498 cell lines growth inhibition was associated with G0/G1 phase arrest and distinct modulation of cell cycle regulating proteins. KTCTL-26 cells were mainly affected by ART through ROS generation, ferroptosis, and decreased metabolism. p53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.
- Addresses
- Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
- Autoren
- Sascha D Markowitsch
- Patricia Schupp
- Julia Lauckner
- Olesya Vakhrusheva
- Kimberly S Slade
- René Mager
- Thomas Efferth
- Axel Haferkamp
- Eva Juengel
- DOI
- 10.3390/cancers12113150
- eISSN
- 2072-6694
- Externe Identifier
- PubMed Identifier: 33121039
- PubMed Central ID: PMC7692972
- Funding acknowledgements
- Friedrich-Spicker-Stiftung: 5
- Open access
- true
- ISSN
- 2072-6694
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Cancers
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2020
- Open access status
- Open Access
- Paginierung
- E3150
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2020
- Titel
- Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 12
Files
https://www.mdpi.com/2072-6694/12/11/3150/pdf?version=1603853757 https://europepmc.org/articles/PMC7692972?pdf=render
Data source: Europe PubMed Central
- Abstract
- Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to investigate the impact of ART (1-100 µM) on the sunitinib-resistant RCC cell lines, Caki-1, 786-O, KTCTL26, and A-498. Therapy-sensitive (parental) and untreated cells served as controls. ART's impact on tumor cell growth, proliferation, clonogenic growth, apoptosis, necrosis, ferroptosis, and metabolic activity was evaluated. Cell cycle distribution, the expression of cell cycle regulating proteins, p53, and the occurrence of reactive oxygen species (ROS) were investigated. ART significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant RCC cells. In Caki-1, 786-O, and A-498 cell lines growth inhibition was associated with G0/G1 phase arrest and distinct modulation of cell cycle regulating proteins. KTCTL-26 cells were mainly affected by ART through ROS generation, ferroptosis, and decreased metabolism. p53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.
- Date of acceptance
- 2020
- Autoren
- Sascha D Markowitsch
- Patricia Schupp
- Julia Lauckner
- Olesya Vakhrusheva
- Kimberly S Slade
- René Mager
- Thomas Efferth
- Axel Haferkamp
- Eva Juengel
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/33121039
- DOI
- 10.3390/cancers12113150
- Externe Identifier
- PubMed Central ID: PMC7692972
- Funding acknowledgements
- Friedrich-Spicker-Stiftung: 5
- ISSN
- 2072-6694
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Cancers (Basel)
- Schlüsselwörter
- Traditional Chinese Medicine (TCM)
- artesunate (ART)
- ferroptosis
- growth inhibition
- reactive oxygen species (ROS)
- renal cell carcinoma (RCC)
- sunitib resistance
- Sprache
- eng
- Country
- Switzerland
- PII
- cancers12113150
- Datum der Veröffentlichung
- 2020
- Status
- Published online
- Titel
- Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 12
Data source: PubMed
- Beziehungen:
- Property of