Cytotoxicity and DNA cross-linking induced by peptide conjugated m-L-sarcolysin in human melanoma cells.

Abstract

Peptichemio is a complex of six peptides containing m-L-sarcolysin which is used in cancer chemotherapy. One of the peptides, L-propyl-m-sarcolysyl-L-p-fluorophenylalanine (PSF), is highly toxic to melanoma cells. We have compared the effects of melphalan, m-L-sarcolysin and PSF on human melanoma cell lines. PSF was 35-fold and 28-fold more toxic to RPMI 8322 melanoma cells than melphalan and m-L-sarcolysin, respectively. Similar differences in the cytotoxic effects of PSF and m-L-sarcolysin were also seen with two other melanoma cell lines. The cytotoxicity of both PSF and m-L-sarcolysin to RPMI 8322 melanoma cells was potentiated by depletion of cellular glutathione. Both PSF and m-L-sarcolysin caused a protracted induction of DNA cross-links in RPMI 8322 cells, with maximum at 24 hours after drug exposure. PSF induced 9-fold higher levels of DNA interstrand cross-links than m-L-sarcolysin, indicating that the increased cytotoxicity of this drug is associated with a more efficient induction of DNA damage.

• Authors: J Hansson, R Lewensohn, U Ringborg
• Journal: Anticancer research (Anticancer Res) 1991 Sep-Oct Vol. 11 Issue 5 Pg. 1725-30 ISSN: 0250-7005 [Print] Greece
• PMID: 1768043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• Dipeptides
• Oligopeptides
• propyl-3-sarcolysin-4-fluorophenylalanine
• metamelfalan
• p-Fluorophenylalanine
• Glutathione
• Melphalan

Topics

• DNA, Neoplasm (drug effects)
• Dipeptides (toxicity)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Glutathione (metabolism)
• Humans
• Melanoma (chemistry, genetics)
• Melphalan (analogs & derivatives, toxicity)
• Oligopeptides
• Tumor Cells, Cultured (drug effects)
• p-Fluorophenylalanine (analogs & derivatives, toxicity)