Titel (eng)

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

Autor*in

Judith Lind   Medical University of Vienna

Karoline Kollmann   University of Veterinary Medicine Vienna

Dagmar Stoiber   Medical University of Vienna / Ludwig Boltzmann Institute for Cancer Research Vienna / Karl Landsteiner University of Health Sciences

Christian W. Gruber   Medical University of Vienna

Sophie Edtmayer   Karl Landsteiner University of Health Sciences

Kathrin Thell   Medical University of Vienna

Jasmin Gattringer   Medical University of Vienna

Herwig P. Moll   Medical University of Vienna

Petra Kudweis   University of Veterinary Medicine Vienna

Roland Hellinger   Medical University of Vienna

Verlag

Elsevier

Beschreibung (eng)

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.

Sprache des Objekts

Englisch

Datum

2022

Rechte

Dieses Werk bzw. dieser Inhalt steht unter einer
CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Klassifikation

Cyclotide Kalata B1; Peripheral T-Cell; Plant Cyclotides; Cycloviolacin O2; Tumor-Suppressor; Viola-Tricolor; Transcriptome; Mechanism; Products; Stat3

Mitglied in der/den Collection(s) (1)