Investigational New Drugs

, Volume 35, Issue 3, pp 260–268

A truncated apoptin protein variant selectively kills cancer cells

  • Santiago Ruiz-Martínez
  • Jessica Castro
  • Maria Vilanova
  • Marta Bruix
  • Douglas V. Laurents
  • Marc Ribó
  • Antoni Benito
PRECLINICAL STUDIES
  • 219 Downloads

Summary

Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However, the use of Apoptin as an anticancer drug is restricted by its strong tendency to aggregate. A number of methods to overcome this problem have been proposed, including transduction techniques to deliver the Apoptin gene into tumor cells, but all such methods have certain drawbacks. Here we describe that a truncated variant of Apoptin, lacking residues 1 to 43, is a soluble, non-aggregating protein that maintains most of the biological properties of wild-type Apoptin when transfected into cells. We show that the cytotoxic effect of this variant is also present when it is added exogenously to cancer cells, but not to normal cells. In addition to the interest this protein has attracted as a promising therapeutic strategy, it is also an excellent model to study the structural properties of Apoptin and how they relate to its mechanism of action.

Keywords

Viral protein Anticancer drug Aggregation Protein engineering Apoptin 

Supplementary material

10637_2017_431_MOESM1_ESM.docx (2.6 mb)
ESM 1(DOCX 2694 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Laboratori d’Enginyeria de Proteïnes, Departament de Biologia, Facultat de CiènciesUniversitat de Girona and Institut d’Investigació Biomèdica de Girona Josep Trueta (IdIBGi)GironaSpain
  2. 2.Instituto de Química Física “Rocasolano”, Consejo Superior de Investigaciones CientíficasMadridSpain

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