Annexin V-targeted enzyme prodrug therapy using cytosine deaminase in combination with 5-fluorocytosine

Cancer Lett. 2011 Aug 1;307(1):53-61. doi: 10.1016/j.canlet.2011.03.016. Epub 2011 May 4.

Abstract

A fusion protein, consisting of cytosine deaminase (CD) linked to human annexin V, was created for use in an enzyme prodrug therapy targeted to the tumor vasculature and associated cancer cells in the primary tumor and distant metastases. The major finding of this study is that the CD-annexin V fusion protein in combination with the prodrug 5-fluorocytosine has significant cytotoxic activity against endothelial cells and two breast cancer cells lines in vitro that expose phosphatidylserine on their surface. The cytotoxicity experiments verified this novel enzyme prodrug system has the ability to produce therapeutic levels of 5-fluorouracil and thus appears promising.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Annexin A5 / genetics*
  • Antimetabolites / pharmacology
  • Aorta / cytology
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Combined Modality Therapy
  • Cytosine Deaminase / genetics*
  • Cytosine Deaminase / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology*
  • Female
  • Flucytosine / pharmacology*
  • Fluorouracil / metabolism
  • Genetic Therapy*
  • Humans
  • Phosphatidylserines / metabolism
  • Prodrugs / pharmacology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Annexin A5
  • Antimetabolites
  • Phosphatidylserines
  • Prodrugs
  • Recombinant Fusion Proteins
  • Flucytosine
  • Cytosine Deaminase
  • Fluorouracil