TY  - JOUR
A1  - Zhao, Fuguang
A1  - Vakhrusheva, Olesya
A1  - Markowitsch, Sascha D.
A1  - Slade, Kimberly S.
A1  - Tsaur, Igor
A1  - Cinatl, Jindrich
A1  - Michaelis, Martin
A1  - Efferth, Thomas
A1  - Haferkamp, Axel
A1  - Jüngel, Eva
T1  - Artesunate impairs growth in cisplatin-resistant bladder cancer cells by cell cycle arrest, apoptosis and autophagy induction
T2  - Cells
N2  - 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.
KW  - bladder cancer (BCa)
KW  - artesunate (ART)
KW  - cisplatin resistance
KW  - growth inhibition
KW  - apoptosis
KW  - autophagy
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57479
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-574796
SN  - 2073-4409
VL  - 9
IS  - Article 2643
PB  - MDPI
CY  - Basel
ER  -