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

Publication ,  Journal Article
Skapek, SX; Colvin, OM; Griffith, OW; Elion, GB; Bigner, DD; Friedman, HS
Published in: Cancer Res
May 15, 1988

The effect and therapeutic consequences of buthionine-(SR)-sulfoximine (BSO)-mediated depletion of glutathione in the human medulloblastoma-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 mumol/g (7.79 +/- 1.61 nmol/mg of protein). Administration i.p. 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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

May 15, 1988

Volume

48

Issue

10

Start / End Page

2764 / 2767

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Methionine Sulfoximine
  • Melphalan
  • Medulloblastoma
 

Citation

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Skapek, S. X., Colvin, O. M., Griffith, O. W., Elion, G. B., Bigner, D. D., & Friedman, H. S. (1988). Enhanced melphalan cytotoxicity following buthionine sulfoximine-mediated glutathione depletion in a human medulloblastoma xenograft in athymic mice. Cancer Res, 48(10), 2764–2767.
Skapek, S. X., O. M. Colvin, O. W. Griffith, G. B. Elion, D. D. Bigner, and H. S. Friedman. “Enhanced melphalan cytotoxicity following buthionine sulfoximine-mediated glutathione depletion in a human medulloblastoma xenograft in athymic mice.Cancer Res 48, no. 10 (May 15, 1988): 2764–67.
Skapek SX, Colvin OM, Griffith OW, Elion GB, Bigner DD, Friedman HS. Enhanced melphalan cytotoxicity following buthionine sulfoximine-mediated glutathione depletion in a human medulloblastoma xenograft in athymic mice. Cancer Res. 1988 May 15;48(10):2764–7.
Skapek SX, Colvin OM, Griffith OW, Elion GB, Bigner DD, Friedman HS. Enhanced melphalan cytotoxicity following buthionine sulfoximine-mediated glutathione depletion in a human medulloblastoma xenograft in athymic mice. Cancer Res. 1988 May 15;48(10):2764–2767.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

May 15, 1988

Volume

48

Issue

10

Start / End Page

2764 / 2767

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Methionine Sulfoximine
  • Melphalan
  • Medulloblastoma