Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Fuguang Zhao
- Olesya Vakhrusheva
- Sascha D Markowitsch
- Kimberly S Slade
- Igor Tsaur
- Jindrich Jr Cinatl
- Martin Michaelis
- Thomas Efferth
- Axel Haferkamp
- Eva Juengel
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000601705200001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/cells9122643
- eISSN
- 2073-4409
- Externe Identifier
- Clarivate Analytics Document Solution ID: PJ3XO
- PubMed Identifier: 33316936
- Ausgabe der Veröffentlichung
- 12
- Zeitschrift
- CELLS
- Schlüsselwörter
- bladder cancer (BCa)
- artesunate (ART)
- cisplatin resistance
- growth inhibition
- apoptosis
- autophagy
- Artikelnummer
- ARTN 2643
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction
- Sub types
- Article
- Ausgabe der Zeitschrift
- 9
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:p>Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1–100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.</jats:p>
- Autoren
- Fuguang Zhao
- Olesya Vakhrusheva
- Sascha D Markowitsch
- Kimberly S Slade
- Igor Tsaur
- Jindrich Cinatl
- Martin Michaelis
- Thomas Efferth
- Axel Haferkamp
- Eva Juengel
- DOI
- 10.3390/cells9122643
- eISSN
- 2073-4409
- Ausgabe der Veröffentlichung
- 12
- Zeitschrift
- Cells
- Sprache
- en
- Online publication date
- 2020
- Paginierung
- 2643 - 2643
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/cells9122643
- Datum der Datenerfassung
- 2020
- Titel
- Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction
- Ausgabe der Zeitschrift
- 9
Data source: Crossref
- Abstract
- Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1-100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.
- Addresses
- Department of Urology and Pediatric Urology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
- Autoren
- Fuguang Zhao
- Olesya Vakhrusheva
- Sascha D Markowitsch
- Kimberly S Slade
- Igor Tsaur
- Jindrich Cinatl
- Martin Michaelis
- Thomas Efferth
- Axel Haferkamp
- Eva Juengel
- DOI
- 10.3390/cells9122643
- eISSN
- 2073-4409
- Externe Identifier
- PubMed Identifier: 33316936
- PubMed Central ID: PMC7763932
- Open access
- true
- ISSN
- 2073-4409
- Ausgabe der Veröffentlichung
- 12
- Zeitschrift
- Cells
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Cell Cycle Proteins
- Microtubule-Associated Proteins
- Medicine, Chinese Traditional
- Apoptosis
- Cell Proliferation
- DNA Repair
- Drug Resistance, Neoplasm
- Autophagy
- Urinary Bladder Neoplasms
- G1 Phase Cell Cycle Checkpoints
- Artesunate
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2020
- Open access status
- Open Access
- Paginierung
- E2643
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2020
- Titel
- Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 9
Files
https://www.mdpi.com/2073-4409/9/12/2643/pdf?version=1607500619 https://europepmc.org/articles/PMC7763932?pdf=render
Data source: Europe PubMed Central
- Abstract
- Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1-100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.
- Date of acceptance
- 2020
- Autoren
- Fuguang Zhao
- Olesya Vakhrusheva
- Sascha D Markowitsch
- Kimberly S Slade
- Igor Tsaur
- Jindrich Cinatl
- Martin Michaelis
- Thomas Efferth
- Axel Haferkamp
- Eva Juengel
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/33316936
- DOI
- 10.3390/cells9122643
- eISSN
- 2073-4409
- Externe Identifier
- PubMed Central ID: PMC7763932
- Ausgabe der Veröffentlichung
- 12
- Zeitschrift
- Cells
- Schlüsselwörter
- apoptosis
- artesunate (ART)
- autophagy
- bladder cancer (BCa)
- cisplatin resistance
- growth inhibition
- Apoptosis
- Artesunate
- Autophagy
- Cell Cycle Proteins
- Cell Line, Tumor
- Cell Proliferation
- DNA Repair
- Drug Resistance, Neoplasm
- G1 Phase Cell Cycle Checkpoints
- Humans
- Medicine, Chinese Traditional
- Microtubule-Associated Proteins
- Urinary Bladder Neoplasms
- Sprache
- eng
- Country
- Switzerland
- PII
- cells9122643
- Datum der Veröffentlichung
- 2020
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 9
Data source: PubMed
- Beziehungen:
- Property of