The effects of a growth-inhibiting tripeptide, acetylGlu-Ser-GlyNH2 (Ac-ESG), on gene expression and cell cycle progression of two lymphoma cell lines

Anticancer Res. 2003 Jul-Aug;23(4):3159-65.

Abstract

Background: We recently isolated and characterized a tripeptide, acetylGlu-Ser-GlyNH2 (Ac-ESG), which inhibits proliferation of lymphoid cells. In this paper we describe the effects of Ac-ESG on growth-related gene expression and cell cycle progression in two lymphoma cell lines, Ramos and Molt, representing B and T lymphocytes, respectively.

Materials and methods: RNA was extracted from Molt and Ramos cells with or without the tripeptide treatment. Gene expression was examined by semi-quantitative RT-PCR and Northern blot hybridization, and cell cycle progression was detected by flow cytometry.

Results: In the Molt cells, p53 gene expression was increased following treatment while c-myc was decreased after treatment shorter than 24 hours; N-ras expression was significantly reduced at picomolar concentration for 24-hour treatment; cyclinD1 and cdk4 expression did not show any change; DNA flow cytometry demonstrated that Molt cells were arrested or delayed predominantly in G2-M. Untreated Ramos cells had higher gene expression levels of c-myc, N-Ras and cdk4 than Molt cells, but lower p53 expression. These cells were not sensitive to Ac-ESG.

Conclusion: The tripeptide Ac-ESG alters the expression of several growth-related genes in the Molt cell line and brings about an arrest or delay of cells in G2-M.

MeSH terms

  • Blotting, Northern
  • Burkitt Lymphoma / drug therapy*
  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / metabolism
  • Burkitt Lymphoma / pathology*
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / biosynthesis
  • Cyclin-Dependent Kinases / genetics
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Flow Cytometry
  • Gene Expression / drug effects
  • Growth Inhibitors / pharmacology
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Leukemia-Lymphoma, Adult T-Cell / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / pathology*
  • Oligopeptides / pharmacology*
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • ras Proteins / biosynthesis
  • ras Proteins / genetics

Substances

  • DNA, Neoplasm
  • Growth Inhibitors
  • N-acetylglutamyl-seryl-glycinamide
  • Oligopeptides
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases
  • ras Proteins