Boosting the anti-tumor activity of natural killer cells by caripe 8 – A Carapichea ipecacuanha isolated cyclotide

List, Julia; Gattringer, Jasmin; Huszarek, Sophie; Marinović, Sonja; Neubauer, Heidi A.; Kudweis, Petra; Putz, Eva-M.; Hellinger, Roland; Gotthardt, Dagmar (2024) Boosting the anti-tumor activity of natural killer cells by caripe 8 – A Carapichea ipecacuanha isolated cyclotide. Biomedicine & Pharmacotherapy, 177 . ISSN 0753-3322

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Abstract

Cyclotides are head-to-tail cyclized peptides with a unique cystine-knot motif. Their structure provides exceptional resistance against enzymatic, chemical, or thermal degradation compared to other peptides. Peptide-based therapeutics promise high specificity, selectivity and lower immunogenicity, making them safer alternatives to small molecules or large biologicals. Cyclotides were researched due to their anti-cancer properties by inducing apoptosis in tumor cells in the past, but the impact of cyclotides on cytotoxic immune cells was poorly studied. Natural Killer (NK) cells are cytotoxic innate lymphoid cells and play an important role in the defense against infected, stressed and transformed cells. NK cells do not need prior sensitization and act in an antigen independent manner, holding promising potential in the field of immunotherapy. To investigate the effect of immunomodulatory cyclotides on NK cells, we evaluated several peptide-enriched plant extracts on NK cell mediated cytotoxicity. We observed that the extract samples derived from Carapichea ipecacuanha (Brot.) L. Andersson augments the killing potential of mouse NK cells against different tumor targets in vitro. Subsequent isolation of cyclotides from C. ipecacuanha extracts led to the identification of a primary candidate that enhances cytotoxicity of both mouse and human NK cells. The augmented killing is facilitated by the increased degranulation capacity of NK cells. In addition, we noted a direct toxic effect of caripe 8 on tumor cells, suggesting a dual therapeutic potential in cancer treatment. This study offers novel insights how natural peptides can influence NK cell cytotoxicity. These pre-clinical findings hold significant promise for advancing current immunotherapeutic approaches.

Item Type:	Article
Uncontrolled Keywords:	NK cells; Anti-tumor activity; Cyclotide; Plant-derived peptide; Carapichea ipecacuanha
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Immunology
Divisions:	Division of Molecular Medicine
Depositing User:	Sonja Marinović
Date Deposited:	09 Aug 2024 07:38
URI:	http://fulir.irb.hr/id/eprint/9003
DOI:	10.1016/j.biopha.2024.117057

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