Title
Boosting the anti-tumor activity of natural killer cells by caripe 8 - A Carapichea ipecacuanha isolated cyclotide
Language
English
Description (en)
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.
Keywords (en)
NK Cells; Anti-Tumor Activity; Cyclotide; Plant-Derived Peptide; Carapichea Ipecacuanha
DOI
10.1016/j.biopha.2024.117057
Author of the digital object
Julia  List  (University of Veterinary Medicine Vienna)
Roland  Hellinger  (Medical University of Vienna)
Dagmar  Gotthardt  (University of Veterinary Medicine Vienna)
Eva-M.  Putz  (University of Veterinary Medicine Vienna)
Petra  Kudweis  (University of Veterinary Medicine Vienna)
Heidi A.  Neubauer  (University of Veterinary Medicine Vienna)
Sonja  Marinovic  (Rudjer Boskovic Institute)
Sophie  Huszarek  (University of Veterinary Medicine Vienna)
Jasmin  Gattringer  (Medical University of Vienna)
Format
application/pdf
Size
9.7 MB
Licence Selected
CC BY 4.0 International
Type of publication
Article
Name of Publication (en)
Biomedicine & Pharmacotherapy
Pages or Volume
15
Volume
177
Publisher
Elsevier
Publication Date
2024
Content
Details
Object type
PDFDocument
Format
application/pdf
Created
04.09.2024 08:36:45
This object is in collection
Metadata
Veterinärmedizinische Universität Wien (Vetmeduni) | Veterinärplatz 1 | 1210 Wien - Österreich | T +43 1 25077-0 | Web: vetmeduni.ac.at