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TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells

Oncogene volume 23, pages 1153–1165 (2004)Cite this article

Abstract

Apoptin has been described to induce apoptosis in various human cancer cell lines, but not in normal cells, thus making it an interesting candidate for the development of novel therapeutic strategies. Apoptin was generated and cloned into several mammalian expression vectors. Transfection or microinjection of apoptin cDNA resulted in its expression, initially in the cytoplasm with a filamentous pattern. Subsequently, apoptin entered the nucleus and efficiently induced apoptosis in several cancer cell lines. Nuclear localization was shown to be required for induction of apoptosis. Apoptin expression level was found to be an important determinant of the efficiency of induction of apoptosis. Surprisingly, expression of apoptin or GFP-apoptin cDNA induced apoptosis in some normal cells. When fused to the HIV-TAT protein transduction domain and delivered as a protein, TAT-apoptin was transduced efficiently (>90%) into normal and tumour cells. However, TAT-apoptin remained in the cytoplasm and did not kill normal 6689 and 1BR3 fibroblasts. In contrast TAT-apoptin migrated from the cytoplasm to the nucleus of Saos-2 and HSC-3 cancer cells resulting in apoptosis after 24 h. This study shows that apoptin is a powerful apoptosis-inducing protein with a potential for cancer therapy.

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Acknowledgements

We are grateful to Dr Daniel Todd (Department of Agriculture and Rural Development for Northern Ireland, the Queen's University of Belfast) for providing pCAA-3 and anti-VP3 monoclonal antibody and for very useful discussions. We are grateful to Dr Steven F Dowdy (Howard Hughes Medical Institute, Department of Pathology, Washington University School of Medicine) for providing pTAT-HA and pTAT-HA-GFP, to Dr Alan Lehmann (MRC Cell Mutation Unit, University of Sussex) for 1BR3 and 1BR3N cells, to Dr Martin Dyer (MRC Toxicology Unit, University of Leicester) for pGFP-Bcl10 and Dr Richard Siegel (NIAID NIH Bethesda) for pFADD-GFP. This study was supported by a grant from the BBSRC (47/GTH12530).

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Authors and Affiliations

  1. Department of Oral Medicine and Pathology, Head and Neck Oncology Group, The Rayne Institute, Guy's, King's and St Thomas' School of Medicine and Dentistry, London, UK

    Lars Guelen, Michelle Meyers & Mahvash Tavassoli

  2. CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, UK

    Hugh Paterson

  3. Department of Molecular Medicine, The Rayne Institute, Guy's, King's and St Thomas' School of Medicine and Dentistry, London, UK

    Joop Gäken & Farzin Farzaneh

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  1. Lars Guelen
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  2. Hugh Paterson
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  6. Mahvash Tavassoli
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Correspondence to Mahvash Tavassoli.

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Guelen, L., Paterson, H., Gäken, J. et al. TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells. Oncogene 23, 1153–1165 (2004). https://doi.org/10.1038/sj.onc.1207224

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