Enhanced melphalan cytotoxicity following buthionine suffoximine-mediated glutathione depletion in a human medulloblastoma xenograft in athymic mice

S. X. Skapek, O. M. Colvin, O. W. Griffith, G. B. Elion, D. D. Bigner, H. S. Friedman

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

The effect and therapeutic consequences of buthionine-(SR)-sulfoxi- (BS0)-mediated depletion of glutathione in the human medullo-blastoma-derived cell line, TE-671, growing as s.c. xenografts in athymic nude mice were examined. The glutathione content of the s.c. xenografts was 1.11 ±0.15 μmol/g (7.79 ± 1.61 nmol/mg of protein). Administration Lp. to tumor-bearing mice of D,L-BSO(two doses at 12-h intervals; 5 mmol/kg) depleted the glutathione content of the xenografts to 25.7% of control Administration of a 30 mM solution of L-BSO in drinking water for 96 h depleted the glutathione content to 17.4% of control Depletion of glutathione with these regimens resulted in a significant increase in the s.c. tumor growth delay over that produced by melphalan alone: 17.2 days versus 12.6 days for D,L-BSO (i.p.) plus melphalan versus melphalan and 22.9 days versus 16.6 days for L-BSO (p.o.) plus melphalan versus melphalan. These studies demonstrate the increased cytotoxicity of melphalan resulting from BSO-mediated depletion of glutathione in human medulloblastoma and support further efforts to modulate the chemosensitivity and radiosensitivity of this tumor by modulation of glutathione.

Original languageEnglish (US)
Pages (from-to)2764-2767
Number of pages4
JournalCancer research
Volume48
Issue number10
StatePublished - May 1988

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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