Artesunate impairs growth in cisplatin-resistant bladder cancer cells by cell cycle arrest, apoptosis and autophagy induction

  • 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.

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Author:Fuguang Zhao, Olesya Vakhrusheva, Sascha D. Markowitsch, Kimberly S. Slade, Igor TsaurORCiDGND, Jindrich CinatlORCiD, Martin MichaelisORCiDGND, Thomas EfferthORCiDGND, Axel HaferkampGND, Eva JüngelORCiDGND
Pubmed Id:
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2020/12/09
Date of first Publication:2020/12/09
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/01/11
Tag:apoptosis; artesunate (ART); autophagy; bladder cancer (BCa); cisplatin resistance; growth inhibition
Issue:Article 2643
Page Number:19
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0