Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

The effects of the tripeptide (acetylGlu-ser-GlyNH2, ESG) from spleen on cell proliferation, gene expressions and cell cycle of lymphoma T and B cells

Y Liu MS 1, WH Reichelt MS 1, K Elgjo MD PhD 2, KL Reichelt MD PhD 1

1 Pediatric Research Institute,, 2 Institute of Pathology, The National Hospital, University of Oslo, Oslo, Norway,

AIMS: we are trying to find the effects of the tripeptide (isolated from spleen) on lymphoma cells proliferation, gene expression and cell cycle. METHODS: tripeptide extraction and purification, cell culture, bioassay, estimation of cell flux into mitosis, Northern blot hybridization, DNA flow cytometry. RESULTS: We found a single-peak fraction (N-acetyl-Glu-Ser-GlyNH2) in water extracts of dog spleen homogenates that inhibited proliferation of Molt (T cell) lymphoma cells at low concentrations in vitro, with no significant effect on a B cell lymphoma cell line (Ramos). The synthetic tripeptide with the same structure decreased the number of cell doublings of Molt cells. In the Molt cells p53 mRNA expression was increased following treatment with the peptide. Short time treatment (2h, 6h, and 24 h) with the peptide induced a decreased c-myc gene expression. Examination of N-ras expression in the Molt cells revealed two electro-phoretically different bands, and showed different responses to peptide treatment. Furthermore, the tripeptide also induced cyclin D and cdk 4 expression in Molt cells. Cell flux and Flow cytometry showed that Molt cells were predominantly arrested in the G2-M phases. CONCLUSIONS: the tripeptide belongs to the oligopeptide growth-inhibiting factors family. the tripeptide related to Molt cells proliferation and some gene expression,, but Ramos cells revealed a much lower susceptibility to the peptide.

KEY WORDS: growth inhibition, lymphocytes, oligopeptide, gene expression.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on cell cycle inhibitors.