The nature inspired peptide [T20K]-kalata B1 induces anti-tumor effects in anaplastic large cell lymphoma

Judith Lind, Roland Hellinger, Petra Kudweis, Herwig E. Moll, Jasmin Gattringer, Kathrin Thell, Sophie Edtmayer, Christian W. Gruber*, Dagmar Stoiber, Karoline Kollmann

*Corresponding author for this work

Research output: Journal article (peer-reviewed)Journal article

Abstract

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.

Original languageEnglish
Article number113486
JournalBiomedicine and Pharmacotherapy
Volume153
DOIs
Publication statusPublished - Sept 2022

Keywords

  • ALCL
  • Apoptosis
  • Circular peptide
  • Leukemia
  • Natural product
  • Animals
  • T-Lymphocytes
  • Humans
  • Cyclotides/pharmacology
  • Mice
  • Cytokines/pharmacology
  • Lymphoma, Large-Cell, Anaplastic/drug therapy

ASJC Scopus subject areas

  • Pharmacology

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