Elsevier 2022 isPartOf:https://phaidra.vetmeduni.ac.at/o:605 Lind, Judith (Medical University of Vienna) Kollmann, Karoline (University of Veterinary Medicine Vienna) Stoiber, Dagmar (Medical University of Vienna / Ludwig Boltzmann Institute for Cancer Research Vienna / Karl Landsteiner University of Health Sciences) Gruber, Christian W. (Medical University of Vienna) Edtmayer, Sophie (Karl Landsteiner University of Health Sciences) Thell, Kathrin (Medical University of Vienna) Gattringer, Jasmin (Medical University of Vienna) Moll, Herwig P. (Medical University of Vienna) Kudweis, Petra (University of Veterinary Medicine Vienna) Hellinger, Roland (Medical University of Vienna) Ribosomally synthesized and post-translationally modified peptides, such as plant cyclotides, are a diverse group of natural products well known as templates in drug discovery and therapeutic lead development. The cyclotide kalata B1 (kB1) has previously been discovered as immunosuppressive agent on T-lymphocytes, and a synthetic version of this peptide, [T20K]kB1 (T20K), has been effective in reducing clinical symptoms, such as inflammation and demyelination, in a mouse model of multiple sclerosis. Based on its T-cell modulatory impact we studied the effects of T20K and several analogs on the proliferation of anaplastic large cell lymphoma (ALCL), a heterogeneous group of clinically aggressive diseases associated with poor prognosis. T20K, as a prototype drug candidate, induces apoptosis and a proliferation arrest in human lymphoma T-cell lines (SR786, Mac-2a and the Jurkat E6.1) in a concentration dependent fashion, at least partially via increased STAT5 and p53 signaling. In contrary to its effect on IL-2 signaling in lymphocytes, the cytokine levels are not altered in lymphoma cells. In vivo mouse experiments revealed a promising activity of T20K on these cancer cells including decreased tumor weight and increased apoptosis. This study opens novel avenues for developing cyclotide-based drug candidates for therapy of patients with ALCL. The nature inspired peptide [T20K]-kalata B1 induces anti-tumor effects in anaplastic large cell lymphoma CC BY 4.0 International http://creativecommons.org/licenses/by/4.0/ doi:10.1016/j.biopha.2022.113486 https://phaidra.vetmeduni.ac.at/o:2075 Biomedicine & Pharmacotherapy 153 (2022) Cyclotide Kalata B1; Peripheral T-Cell; Plant Cyclotides; Cycloviolacin O2; Tumor-Suppressor; Viola-Tricolor; Transcriptome; Mechanism; Products; Stat3 eng article application/pdf