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Saporin as a novel suicide gene in anticancer gene therapy

Cancer Gene Therapy volume 14, pages 165–173 (2007)Cite this article

A Corrigendum to this article was published on 11 April 2007

Abstract

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 × 104 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.

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Acknowledgements

We thank Angelo Corti, Paolo Dellabona and David Flavell for fruitful discussions. This study was partially supported by the Italian Cancer Research Association (AIRC).

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Author notes

  1. R Vago

    Present address: Istituto di Genetica Molecolare, CNR, Pavia, Italy

  2. T Soldà

    Present address: Istituto per la Ricerca Biomedica, Bellinzona, Switzerland

  3. L Monaco

    Present address: Telethon Onlus, Scientific Office, Milan, Italy

  4. M S Fabbrini

    Present address: Istituto Biologia e Biotecnologia Agraria, IBBA, CNR, via Bassini, Milan, 15 20133, Italy

  5. N Zarovni and R Vago: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological and Technological Research and Cancer Immunotherapy and Gene Therapy Program, San Raffaele H Scientific Institute, Milan, Italy

    N Zarovni, R Vago, T Soldà, L Monaco & M S Fabbrini

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Correspondence to M S Fabbrini.

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Zarovni, N., Vago, R., Soldà, T. et al. Saporin as a novel suicide gene in anticancer gene therapy. Cancer Gene Ther 14, 165–173 (2007). https://doi.org/10.1038/sj.cgt.7700998

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