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The Antimicrobial Peptide γ-Thionin from Habanero Chile (Capsicum chinense) Induces Caspase-Independent Apoptosis on Human K562 Chronic Myeloid Leukemia Cells and Regulates Epigenetic Marks.
Flores-Alvarez, Luis José; Jiménez-Alcántar, Paola; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E.
Afiliação
  • Flores-Alvarez LJ; Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km 9.5 Carretera Morelia-Zinapécuaro, Posta Veterinaria, Morelia C.P. 58893, Mexico.
  • Jiménez-Alcántar P; Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km 9.5 Carretera Morelia-Zinapécuaro, Posta Veterinaria, Morelia C.P. 58893, Mexico.
  • Ochoa-Zarzosa A; Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km 9.5 Carretera Morelia-Zinapécuaro, Posta Veterinaria, Morelia C.P. 58893, Mexico.
  • López-Meza JE; Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Km 9.5 Carretera Morelia-Zinapécuaro, Posta Veterinaria, Morelia C.P. 58893, Mexico.
Molecules ; 28(9)2023 Apr 23.
Article em En | MEDLINE | ID: mdl-37175071
Cancer is a relevant health problem worldwide. In 2020, leukemias represented the 13th most commonly reported cancer cases worldwide but the 10th most likely to cause deaths. There has been a progressive increase in the efficacy of treatments for leukemias; however, these still generate important side effects, so it is imperative to search for new alternatives. Defensins are a group of antimicrobial peptides with activity against cancer cells. However, the cytotoxic mechanism of these peptides has been described mainly for animal defensins. This study shows that defensin γ-thionin (Capsicum chinense) is cytotoxic to the K562 leukemia cells with an IC50 = 290 µg/mL (50.26 µM) but not for human peripheral blood mononuclear cells. Results showed that γ-thionin did not affect the membrane potential; however, the peptide modified the mitochondrial membrane potential (ΔΨm) and the intracellular calcium release. In addition, γ-thionin induced apoptosis in K562 cells, but the activation of caspases 8 and 9 was not detected. Moreover, the activation of calpains was detected at one hour of treatment, suggesting that γ-thionin activates the caspase-independent apoptosis. Furthermore, the γ-thionin induced epigenetic modifications on histone 3 in K562 cells, increased global acetylation (~2-fold), and specific acetylation marks at lysine 9 (H3K9Ac) (~1.5-fold). In addition, γ-thionin increased the lysine 9 methylation (H3K9me) and dimethylation marks (H3K9me2) (~2-fold), as well as the trimethylation mark (H3K9me3) (~2-fold). To our knowledge, this is the first report of a defensin that triggers caspase-independent apoptosis in cancer cells via calpains and regulating chromatin remodelation, a novel property for a plant defensin.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Capsicum / Leucemia Mielogênica Crônica BCR-ABL Positiva / Tioninas / Antineoplásicos Limite: Animals / Humans País/Região como assunto: America do sul / Chile Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: México País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Capsicum / Leucemia Mielogênica Crônica BCR-ABL Positiva / Tioninas / Antineoplásicos Limite: Animals / Humans País/Região como assunto: America do sul / Chile Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: México País de publicação: Suíça