IL13 fused pseudomonas exotoxin targets various cancers in vitro

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dc.authorid0000-0002-9096-1512
dc.contributor.authorUludağ, Damla
dc.contributor.authorKarakaş, Nihal
dc.date.accessioned2021-08-02T11:44:09Z
dc.date.available2021-08-02T11:44:09Z
dc.date.issued2021
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.departmentİstanbul Medipol Üniversitesi, Sağlık Bilimleri Enstitüsü, Tıbbi Biyoloji ve Genetik Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.description.abstractBackground/Aim: Pseudomonas exotoxin (PE) is one of the most widely used toxins in the construction of therapeutic fusion proteins in pre-clinical studies followed by phase trials. In principle, PE acts by blocking protein synthesis through catalyzing the inactivation of elongation factor-2 (EF-2). The interleukin-13 fused PE (IL13-PE) cytotoxin was previously designed to target GBM cells. In this study, the cytotoxic effects of IL13-PE were evaluated in 5 different types of cancers and the therapeutic effects were further analyzed in a lung cancer cell line, NCI-H460. Conceptually, in another lung cancer cell line (A549), ILI 3R alpha 2 was overexpressed by lentiviruses (A549-IL13R alpha 2) and evaluated for cytotoxic efficacy of IL13-PE. Materials and Methods: The expression profile of IL13R alpha 2 in different cancer cell lines was determined by RT-PCR. Secretable toxin fusion was expressed in the toxin resistant HEK-293T cell line (293T-TxR) by using a plasmid coding for IL13-PE and IRESGFP (LV-IL13-PE-IRESIGFP). Next, the cells were shown to produce and secrete functional ILI3-PE by dot blot analysis, followed by cell viability assays and cell death analysis. Results: Upon treatment with IL13-PE, a significant decrease in cell viability was selectively demonstrated in cancer cells with cognate receptor expression. IL13-PE treatment increased the apoptoticlnecrotic cell populations in the NCIH460 cell line. Conclusion: Our results demonstrate that IL13-PE can be a therapeutic target for tumors bearing mostly IL13R alpha 2 positive cell populations. Our findings also suggest a cell-based delivery option for the recombinant toxins in the treatment of different cancers which can provide a solution for the clinical use of toxin therapy.
dc.identifier.citationUludağ, D. ve Karakaş, N. (2021). IL13 fused pseudomonas exotoxin targets various cancers in vitro. Anticancer Research, 41(7), 3471-3480. https://dx.doi.org/10.21873/anticanres.15134
dc.identifier.doi10.21873/anticanres.15134
dc.identifier.endpage3480
dc.identifier.issn0250-7005
dc.identifier.issn1791-7530
dc.identifier.issue7
dc.identifier.scopusqualityQ2
dc.identifier.startpage3471
dc.identifier.urihttps://dx.doi.org/10.21873/anticanres.15134
dc.identifier.urihttps://hdl.handle.net/20.500.12511/7646
dc.identifier.volume41
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherInternational Institute of Anticancer Research
dc.relation.ispartofAnticancer Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/117S421
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectCancer
dc.subjectIL13
dc.subjectIL13R?2
dc.subjectPseudomonas Exotoxin
dc.subjectRecombinant Toxin
dc.subjectToxin
dc.titleIL13 fused pseudomonas exotoxin targets various cancers in vitro
dc.typeArticle

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