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

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.