Apoptin, A Versatile Protein with Selective Antitumor Activity

Curr Med Chem. 2018;25(30):3540-3559. doi: 10.2174/0929867325666180309112023.

Abstract

Background: Research in the field of antitumor chemotherapeutics pursues a key issue, drug selectivity for cancer cells. In the last 20 years, a group of proteins has attracted scientific interest as cancer chemotherapeutics due to their ability to specifically kill cancer cells while leaving normal cells undamaged. One of these proteins is apoptin.

Methods: In this study, the recent available literature regarding cell death mechanisms induced by apoptin has been reviewed. Delivering this drug to tumor cells is a challenge because it spontaneously forms soluble non-covalent aggregates. This led us to include in this review the different approaches for obtaining the maximum efficiency of apoptin entry to cancer cells.

Results: This review provides an up-to-date summary of the mechanisms by which apoptin induces selective apoptosis in tumor cells while leaving normal cells undamaged. It highlights the relationship between the apoptosis mechanism induced by this protein and its functional motifs. Apoptin has been described as an intrinsically disordered protein, which explains its ability to interact with multiple partners and affect multiple pathways inside the cell. Characterization of the different partners and pathways induced by apoptin has begun to shed light on the molecular basis of apoptin's tumor-selective cytotoxicity.

Conclusion: The findings confirm the interest in apoptin as a potentially safe antitumor drug. Research still needed to be conducted to find an effective way to deliver apoptin for use in clinics.

Keywords: Apoptin; DNA damage response; antitumor drug; apoptosis; cancer; viral protein..

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Capsid Proteins / chemistry
  • Capsid Proteins / metabolism
  • Capsid Proteins / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cyclin-Dependent Kinases / chemistry
  • Cyclin-Dependent Kinases / metabolism
  • DNA / chemistry
  • DNA / metabolism
  • DNA Damage / drug effects
  • Drug Carriers / chemistry
  • Humans
  • Neoplasms / metabolism
  • Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Capsid Proteins
  • Drug Carriers
  • VP3 protein, Chicken anemia virus
  • DNA
  • Cyclin-Dependent Kinases