Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis

摘要

Renal cell carcinoma (RCC) is the most common kidney malignancy. Due to development of therapy resistance, efficacy of conventional drugs such as sunitinib is limited. Artesunate (ART), a drug originating from Traditional Chinese Medicine, has exhibited anti-tumor effects in several non-urologic tumors. ART inhibited growth, reduced metastatic properties, and curtailed metabolism in sunitinib-sensitive and sunitinib–resistant RCC cells. In three of four tested cell lines, ART’s growth inhibitory effects were accompanied by cell cycle arrest and modulation of cell cycle regulating proteins. In a fourth cell line, KTCTL-26, ART evoked ferroptosis, an iron-dependent cell death, and exhibited stronger anti-tumor effects than in the other cell lines. The regulatory protein, p53, was only detectable in the KTCTL-26 cells, possibly making p53 a predictive marker of cancer that may respond better to ART. ART, therefore, may hold promise as an additive therapy option for selected patients with advanced or therapy-resistant RCC.