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Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca^(2+) Signaling
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作者 Lucas dos Santos Zamarioli Michele Rosana Maia Santos +7 位作者 Adolfo Garcia Erustes Vanessa Marques Meccatti Thais Cristine Pereira Soraya S Smaili Maria Cristina Marcucci Carlos Rocha Oliveira Gustavo JS Pereira Claudia Bincoletto 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2024年第6期525-533,共9页
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 Ph... 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 Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)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 Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV. 展开更多
关键词 Artemisia vulgaris NECROPTOSIS ferroptosis late apoptosis Ca^(2+)signaling
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