首页|Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+Signaling
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+Signaling
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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＜0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P＜0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P＜0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P＜0.01).HEAV-induced Ca2+release mainly from lysosomes in K562 cells(P＜0.01).Furthermore,BAPTA-AM,an intracellular Ca2+chelator,decreased the number of non-viable cells treated with HEAV(P＜0.05).Conclusions:HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca2+.These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.
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