o:2075 The nature inspired peptide [T20K]-kalata B1 induces anti-tumor effects in anaplastic large cell lymphoma en 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. Cyclotide Kalata B1; Peripheral T-Cell; Plant Cyclotides; Cycloviolacin O2; Tumor-Suppressor; Viola-Tricolor; Transcriptome; Mechanism; Products; Stat3 1552099 10.1016/j.biopha.2022.113486 2023-09-05T14:11:02.277Z 44 yes 46 Judith Lind Medical University of Vienna Roland Hellinger Medical University of Vienna person Petra Kudweis University of Veterinary Medicine Vienna person Herwig P. Moll Medical University of Vienna person Jasmin Gattringer Medical University of Vienna person Kathrin Thell Medical University of Vienna person Sophie Edtmayer Karl Landsteiner University of Health Sciences person Christian W. Gruber Medical University of Vienna person Dagmar Stoiber Medical University of Vienna / Ludwig Boltzmann Institute for Cancer Research Vienna / Karl Landsteiner University of Health Sciences person Karoline Kollmann University of Veterinary Medicine Vienna person 0000-0002-7937-4245 application/pdf 808560 https://phaidra.vetmeduni.ac.at/o:2075 no yes 16 70 1552253 Biomedicine & Pharmacotherapy 10 153 Elsevier 2022