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.

Abstract

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.

• Authors: Luis José Flores-Alvarez, Paola Jiménez-Alcántar, Alejandra Ochoa-Zarzosa, Joel E López-Meza
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 28 Issue 9 (Apr 23 2023) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 37175071 (Publication Type: Journal Article)

Chemical References

• Thionins
• Antimicrobial Peptides
• Lysine
• Peptides
• Antineoplastic Agents
• Caspases
• Defensins

Topics

• Animals
• Humans
• Thionins (pharmacology)
• K562 Cells
• Capsicum (chemistry)
• Antimicrobial Peptides
• Chile
• Leukocytes, Mononuclear (metabolism)
• Lysine (pharmacology)
• Apoptosis
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Peptides (pharmacology)
• Antineoplastic Agents (pharmacology)
• Caspases (metabolism)
• Defensins (pharmacology)
• Epigenesis, Genetic