Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling

Abstract

Objective To evaluate the chemical composition and effects of Artemisia vulgaris (AV) hydroalcoholic extract (HEAV) on breast cancer cells (MCF-7 and SKBR-3), chronic myeloid leukemia (K562) and NIH/3T3 fibroblasts. Methods Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass (HPLC) spectrometry. Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD, respectively. Ferrostatin-1 (Fer-1) and necrostatin-1 (Nec-1) were used to assess the mode of HEAV-induced cell death and acetoxymethylester (BAPTA-AM) was used to verify the involvement of cytosolic calcium in this event. Cytosolic calcium measurements were made using Fura-2-AM. Results HEAV decreased the viability of MCF-7, SKBR-3 and K562 cells (P 2+ release mainly from lysosomes in K562 cells (P 2+ chelator, decreased the number of non-viable cells treated with HEAV (P Conclusions HEAV is cytotoxic and activates several modalities of cell death, which are partially dependent on lysosomal release of Ca 2+ . These effects may be related to artemisinin and caffeoylquinic acids, the main compounds identified in HEAV.