Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells

Br J Cancer. 2000 Sep;83(6):800-10. doi: 10.1054/bjoc.2000.1353.


The effects of arginine deprivation (-Arg) has been examined in 26 cell lines. Less than 10% of those with transformed or malignant phenotype survived for > 5 days, and many died more rapidly, notably leukaemic cells. Bivariate flow cytometry confirmed that vulnerable cell lines failed to move out of cell cycle into a quiescent state (G0), but reinitiated DNA synthesis. Many cells remained in S-phase, and/or had difficulty progressing through to G2 and M. Two tumour lines proved relatively 'resistant', A549 and MCF7. Although considerable cell loss occurred initially, both lines showed a 'cell cycle freeze', in which cells survived for > 10 days. These cells recovered their proliferative activity in +Arg medium, but behaved in the same manner to a second -Arg episode as they did to the first episode. In contrast, normal cells entered G0 and survived in -Arg medium for several weeks, with the majority of cells recovering with predictable kinetics in +Arg medium. In general, cells from a wide range of tumours and established lines die quickly in vitro following -Arg treatment, because of defective cell cycle checkpoint stringency, the efficacy of the treatment being most clearly demonstrated in co-cultures in which only the normal cells survived. The findings demonstrate a potentially simple, effective and non-genotoxic strategy for the treatment of a wide range of cancers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Arginine / metabolism*
  • Cell Cycle
  • Cell Line, Transformed
  • Culture Media
  • Dipodomys
  • Flow Cytometry
  • Humans
  • Mice
  • Mink
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Tumor Cells, Cultured


  • Culture Media
  • Arginine