Artesunate Exhibits Synergy With Cisplatin and Cytotoxicity for Upper Tract and Bladder Urothelial Carcinoma Cells

Abstract

Background/aim: Urothelial carcinoma (UC) may arise from the urothelium of the upper tract and the bladder. Cisplatin-based therapy remains the gold standard for UC treatment. The poor 5-year survival rate of UC patients creates an urgent need to develop new drugs for advanced UC therapy. Artesunate (ART), a traditional Chinese medicine for treating malaria, is a potential anticancer agent, but its antigrowth effects on upper tract and bladder UC have not been investigated.

Materials and methods: The antigrowth effect of ART in HT 1376 (bladder UC cells) and BFTC 909 [upper tract urothelial carcinoma (UTUC) cells] was determined by the CCK-8 assay. Flow cytometric analysis was used to evaluate the cell cycle distribution and apoptosis. The cell cycle, apoptosis, and autophagy-related protein expression were analyzed by western blotting. The efficacy of combination treatment with cisplatin was determined by the Calcusyn software.

Results: ART induced HT 1376 and BFTC 909 cell death in a concentration- and time-dependent manner, inducing G₂/M cell-cycle arrest. ART induced apoptosis and redox imbalance in HT 1376 and BFTC 909 cells. Application of the reactive oxygen species (ROS) scavenger, N-acetyl-L-cysteine (NAC), attenuated cell death in ART-treated UC cells. BFTC 909 cells show a better response after ART treatment.

Conclusion: ART may be a candidate drug for treating UTUC and bladder UC while increasing the therapeutic effect of cisplatin.

Keywords: Artesunate; ROS; cisplatin; synergy; urothelial carcinoma.