Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling
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 chromat...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | Brasil |
| Institución: | Universidade Estadual Paulista (UNESP) |
| Repositorio: | Repositório Institucional da UNESP |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unesp.br:11449/309078 |
| Acceso en línea: | http://dx.doi.org/10.1007/s11655-023-3712-2 https://hdl.handle.net/11449/309078 |
| Access Level: | acceso abierto |
| Palabra clave: | Artemisia vulgaris Ca2+ signaling ferroptosis late apoptosis necroptosis |
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Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ SignalingArtemisia vulgarisCa2+ signalingferroptosislate apoptosisnecroptosisObjective: 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.Department of Pharmacology Paulista School of Medicine Federal University of São Paulo, SPResearch Group on Phytocomplexes and Cell Signaling School of Health Sciences Anhembi Morumbi University, SPDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (ICT-UNESP), SPDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (ICT-UNESP), SPUniversidade de São Paulo (USP)Anhembi Morumbi UniversityUniversidade Estadual Paulista (UNESP)2025-04-29T20:14:21Z2024-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article525-533http://dx.doi.org/10.1007/s11655-023-3712-2Chinese Journal of Integrative Medicine, v. 30, n. 6, p. 525-533, 2024.1993-04021672-0415https://hdl.handle.net/11449/30907810.1007/s11655-023-3712-22-s2.0-85178227217Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengChinese Journal of Integrative Medicineinfo:eu-repo/semantics/openAccessZamarioli, Lucas dos SantosSantos, Michele Rosana MaiaErustes, Adolfo GarciaMeccatti, Vanessa Marques [UNESP]Pereira, Thaís Cristine [UNESP]Smaili, Soraya S.Marcucci, Maria Cristina [UNESP]Oliveira, Carlos RochaPereira, Gustavo J. S.Bincoletto, Claudia2025-04-30T13:35:37Zoai:repositorio.unesp.br:11449/309078Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462025-04-30T13:35:37Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
| dc.title.none.fl_str_mv |
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling |
| title |
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling |
| spellingShingle |
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling Zamarioli, Lucas dos Santos Artemisia vulgaris Ca2+ signaling ferroptosis late apoptosis necroptosis |
| title_short |
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling |
| title_full |
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling |
| title_fullStr |
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling |
| title_full_unstemmed |
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling |
| title_sort |
Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling |
| dc.creator.none.fl_str_mv |
Zamarioli, Lucas dos Santos Santos, Michele Rosana Maia Erustes, Adolfo Garcia Meccatti, Vanessa Marques [UNESP] Pereira, Thaís Cristine [UNESP] Smaili, Soraya S. Marcucci, Maria Cristina [UNESP] Oliveira, Carlos Rocha Pereira, Gustavo J. S. Bincoletto, Claudia |
| author |
Zamarioli, Lucas dos Santos |
| author_facet |
Zamarioli, Lucas dos Santos Santos, Michele Rosana Maia Erustes, Adolfo Garcia Meccatti, Vanessa Marques [UNESP] Pereira, Thaís Cristine [UNESP] Smaili, Soraya S. Marcucci, Maria Cristina [UNESP] Oliveira, Carlos Rocha Pereira, Gustavo J. S. Bincoletto, Claudia |
| author_role |
author |
| author2 |
Santos, Michele Rosana Maia Erustes, Adolfo Garcia Meccatti, Vanessa Marques [UNESP] Pereira, Thaís Cristine [UNESP] Smaili, Soraya S. Marcucci, Maria Cristina [UNESP] Oliveira, Carlos Rocha Pereira, Gustavo J. S. Bincoletto, Claudia |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Anhembi Morumbi University Universidade Estadual Paulista (UNESP) |
| dc.subject.por.fl_str_mv |
Artemisia vulgaris Ca2+ signaling ferroptosis late apoptosis necroptosis |
| topic |
Artemisia vulgaris Ca2+ signaling ferroptosis late apoptosis necroptosis |
| description |
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. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024-06-01 2025-04-29T20:14:21Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1007/s11655-023-3712-2 Chinese Journal of Integrative Medicine, v. 30, n. 6, p. 525-533, 2024. 1993-0402 1672-0415 https://hdl.handle.net/11449/309078 10.1007/s11655-023-3712-2 2-s2.0-85178227217 |
| url |
http://dx.doi.org/10.1007/s11655-023-3712-2 https://hdl.handle.net/11449/309078 |
| identifier_str_mv |
Chinese Journal of Integrative Medicine, v. 30, n. 6, p. 525-533, 2024. 1993-0402 1672-0415 10.1007/s11655-023-3712-2 2-s2.0-85178227217 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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Chinese Journal of Integrative Medicine |
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info:eu-repo/semantics/openAccess |
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openAccess |
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525-533 |
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Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
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Universidade Estadual Paulista (UNESP) |
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UNESP |
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UNESP |
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Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
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15.228081 |