Saporin as a novel suicide gene in anticancer gene therapy
| Autor: | T Soldà, Maria Serena Fabbrini, L Monaco, Riccardo Vago, Natasa Zarovni |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
genetic structures Saporin Genetic enhancement Mutant Melanoma Experimental Gene delivery terapia di espressione suicida Catalysis Mice melanoma Animals vettori non retrovirali Luciferase Molecular Biology Plant Proteins terapia genica biology Genes Transgenic Suicide Promoter Genetic Therapy Suicide gene Molecular biology Lipofectamine biology.protein Molecular Medicine Saporina |
| Zdroj: | Cancer gene therapy 14 (2007): 165–173. info:cnr-pdr/source/autori:Zarovni N., Vago R., Soldà T., Monaco L., Fabbrini M.S./titolo:Saporin as a novel suicide gene in anticancer gene therapy/doi:/rivista:Cancer gene therapy/anno:2007/pagina_da:165/pagina_a:173/intervallo_pagine:165–173/volume:14 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700998 |
| Popis: | We used a non-viral gene delivery approach to explore the potential of the plant saporin (SAP) gene as an alternative to the currently employed suicide genes in cancer therapy. Plasmids expressing cytosolic SAP were generated by placing the region encoding the mature plant ribosome-inactivating protein under the control of cytomegalovirus (CMV) or simian virus 40 (SV40) promoters. Their ability to inhibit protein synthesis was first tested in cultured tumor cells co-transfected with a luciferase reporter gene. In particular, SAP expression driven by CMV promoter (pCI-SAP) demonstrated that only 10 ng of plasmid per 1.6 x 10(4) B16 cells drastically reduced luciferase activity to 18% of that in control cells. Direct intratumoral injection of pCI-SAP complexed with either lipofectamine or N-(2,3-dioleoyloxy-1-propyl) trimethylammonium methyl sulfate (DOTAP) in B16 melanoma-bearing mice resulted in a noteworthy attenuation of tumor growth. This antitumor effect was increased in mice that received repeated intratumoral injections. A SAP catalytic inactive mutant (SAP-KQ) failed to exert any antitumor effect demonstrating that this was specifically owing to the SAP N-glycosidase activity. Our overall data strongly suggest that the gene encoding SAP, owing to its rapid and effective action and its independence from the proliferative state of target cells might become a suitable candidate suicide gene for oncologic applications. |
| Databáze: | OpenAIRE |
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