In Vitro Ferroptotic and Antitumor Effect of Free or Liposome-Encapsulated Artesunate in Papillary Thyroid Cancer Cells.

Papillary thyroid cancer (PTC) is generally treated as an indolent and curable cancer. However, the unavailability of surgery and ineffective radiotherapy persists in PTCs, resulting in poor outcomes and low survival rates. Thus, new chemotherapeutic strategies for PTCs are urgently needed. Resistance to ferroptosis remarkably contributes to cancer occurrence and progression. Artesunate (ART) has been repurposed as an anticancer drug, as it induces cell death in numerous cancers. However, whether ART induces ferroptosis in PTC cells and, consequently, facilitates PTC therapy remains elusive. Furthermore, overcoming the pharmacological limitations of ART is a key requirement to support its clinical application. Herein, we reanalyzed the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression database (GTEx) to characterize the occurrence of resistance to ferroptosis in thyroid cancer. In vitro results showed that ART induced ferroptosis in PTC cells by increasing the cellular iron content. The encapsulation of ART by liposomes did not alter the efficiency in inducing ferroptosis and inhibiting the invasion and migration of PTC cells compared with direct ART application. Thus, PTC resistance to ferroptosis can be overcome by ART and liposome-encapsulated ART.