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

*Korrespondierende:r Autor:in für diese Arbeit

Publikation: Beitrag in Fachzeitschrift (peer-reviewed)Artikel in Fachzeitschrift

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.

OriginalspracheEnglisch
Aufsatznummer113486
FachzeitschriftBiomedicine and Pharmacotherapy
Jahrgang153
DOIs
PublikationsstatusVeröffentlicht - Sept. 2022

ASJC Scopus Sachgebiete

  • Pharmakologie

Fingerprint

Untersuchen Sie die Forschungsthemen von „The nature inspired peptide [T20K]-kalata B1 induces anti-tumor effects in anaplastic large cell lymphoma“. Zusammen bilden sie einen einzigartigen Fingerprint.

Dieses zitieren