L-arginine enhances arginine deiminase induced human lymphoma cell growth inhibition through NF-kBp65 and p53 expression in vitro

Eur Rev Med Pharmacol Sci. 2014;18(15):2124-31.

Abstract

Objective: Arginine deiminase (ADI) and L-arginine (L-Arg) can act as anti-tumor agents in-vitro and in-vivo. However, the mechanism of ADI and L-Arg as anti-tumor agents has not been clearly shown.

Materials and methods: With the goal of understanding the role of ADI and L-Arg in inhibition of cell growth, we used the Ramos human lymphoma cell line, which is known to be ADI-sensitive, and observed the p53 and NF-κBp65 protein expression after ADI and arginine treatment. After determining an optimal experimental ADI concentration (0.01 U/ml), we studied the effects of ADI treatment, when combined with different concentrations of L-arginine (control, ADI only, ADI with 10 mM/ml Arg, ADI with 30 mM/ml Arg, and ADI with 50 mM/ml Arg). An MTT assay was used to assess cell survival after treatment, Western blot analysis to determine the levels of the NF-κBp65, p53 and NO mediators and nitric oxide assays were used to determine nitrite levels.

Results and conclusions: L-arginine enhanced ADI-induced inhibited cell growth through expression of NF-κBp65 and p53 in a dose-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Arginine / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Hydrolases / pharmacology*
  • Lymphoma / drug therapy*
  • Lymphoma / metabolism
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Tumor Suppressor Protein p53
  • Nitric Oxide
  • Arginine
  • Hydrolases
  • arginine deiminase