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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

Molecules (Basel, Switzerland), 2023-04, Vol.28 (9), p.3661 [Periódico revisado por pares]

Switzerland: MDPI AG

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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
Autor: Flores-Alvarez, Luis José ; Jiménez-Alcántar, Paola ; Ochoa-Zarzosa, Alejandra ; López-Meza, Joel E
Assuntos: Acetylation ; Animals ; Antiinfectives and antibacterials ; Antimicrobial Peptides ; Antineoplastic Agents - pharmacology ; Apoptosis ; Calcium (intracellular) ; calpains ; Cancer ; Capsicum - chemistry ; Capsicum chinense ; Caspase ; Caspases - metabolism ; Cell activation ; Chile ; Chromatin ; Chronic myeloid leukemia ; Cytotoxicity ; Defensins ; Defensins - pharmacology ; Epigenesis, Genetic ; Epigenetic inheritance ; epigenetic regulation ; Epigenetics ; Histones ; Humans ; K562 Cells ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - metabolism ; Lysine ; Lysine - pharmacology ; Membrane potential ; Membranes ; Methylation ; Mitochondria ; Myeloid leukemia ; Peptides ; Peptides - pharmacology ; Peripheral blood mononuclear cells ; Phosphorylation ; Thionins - pharmacology ; Tumor necrosis factor-TNF ; γ-thionin
É parte de: Molecules (Basel, Switzerland), 2023-04, Vol.28 (9), p.3661
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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 ( ) is cytotoxic to the K562 leukemia cells with an IC = 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.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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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

Switzerland: MDPI AG

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