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Targeting of the Interleukin-13 Receptor (IL-13R)α2 Expressing Prostate Cancer by a Novel Hybrid Lytic Peptide

Paula Row, Riaz Jannoo, Zhidao Xia, Paula E. Row, Venkat Kanamarlapudi Orcid Logo

Biomolecules, Volume: 13, Issue: 2, Start page: 356

Swansea University Authors: Paula Row, Venkat Kanamarlapudi Orcid Logo

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DOI (Published version): 10.3390/biom13020356

Abstract

The IL-13Rα2 cell surface receptor is highly expressed in tumours such as prostate cancer. In this report, we evaluated the hypothesis that prostate cancer cells with enhanced IL-13Rα2 expression are a suitable target for the hybrid lytic peptide (Pep-1-Phor21) peptide, which is generated by fusing...

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Published in: Biomolecules
ISSN: 2218-273X
Published: MDPI AG 2023
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa63097
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Abstract: The IL-13Rα2 cell surface receptor is highly expressed in tumours such as prostate cancer. In this report, we evaluated the hypothesis that prostate cancer cells with enhanced IL-13Rα2 expression are a suitable target for the hybrid lytic peptide (Pep-1-Phor21) peptide, which is generated by fusing the IL-13Rα2 specific ligand (Pep-1) and a cell membrane disrupting lytic peptide (Phor21). The expression of IL-13Rα2 mRNA and protein in prostate cancer tissues and cell lines was assessed via real-time PCR (RT-PCR) and immunoblotting. The effect of Pep-1-Phor21 on the viability of prostate cancer cells grown in monolayers (2D) and microtissue spheroids (3D) was assessed via CellTox green cytotoxic assay. IL-13Rα2 expression and Pep-1-Phor21-mediated killing were also determined in the cells treated with epigenetic regulators (Trichostatin A (TSA) and 5-aza-2 deoxycytidine (5-Aza-dC)). The hybrid lytic peptide cytotoxic activity correlated with the expression of IL-13Rα2 in prostate cancer cell lines cultured as monolayers (2D) or 3D spheroids. In addition, TSA or 5-Aza-dC treatment of prostate cancer cells, particularly those with low expression of IL-13Rα2, enhanced the cells' sensitivity to the lytic peptide by increasing IL-13Rα2 expression. These results demonstrate that the Pep-1-Phor21 hybrid lytic peptide has potent and selective anticancer properties against IL-13Rα2-expressing prostate cancer cells.
Keywords: 3D spheroids; IL-13Rα2; Pep-1; Phor21; epigenetics; hybrid lytic peptide; prostate cancer; therapeutic peptide
College: Faculty of Medicine, Health and Life Sciences
Issue: 2
Start Page: 356