Total Methionine Restriction Treatment of Cancer

Robert M. Hoffman, Demetrius M. Kokkinakis, Eugene P Frenkel

Research output: Contribution to journalArticle

Abstract

This chapter reviews how total methionine (MET) restriction (MR) of a human brain tumor xenograft, effected by the combination of recombinant L-methionine-α-deamino-γ-lyase (rMETase) and a MET-free diet, greatly potentiates standard chemotherapy for brain tumors in mouse models. The growth of human brain tumor Daoy, SWB77, and D-54 xenografts in nude mice was arrested after the depletion of mouse plasma methionine (MET) with a combination of an MR diet and rMETase and homocysteine to rescue normal cells and tissues. MET was depleted to below 5 μm by this treatment. MR for 10-12 days inhibited tumor growth, but did not prevent tumor regrowth after treatment cessation. A single dose of N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), which was ineffective alone, was administered at the end of the MR regimen, and caused a more than 80-day growth delay for Daoy and D-54 and a 20-day growth delay for SWB77. The total MR treatment regimens also increased the efficacy of temozolomide (TMZ) against the SWB77 xenograft when administered at the end of the MET regimen.

Original languageEnglish (US)
Pages (from-to)163-171
Number of pages9
JournalMethods in molecular biology (Clifton, N.J.)
Volume1866
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Methionine
Heterografts
Brain Neoplasms
Carmustine
Neoplasms
temozolomide
Growth
Therapeutics
Diet
Withholding Treatment
Lyases
Homocysteine
Nude Mice
Drug Therapy

Keywords

  • BCNU
  • Cancer
  • Choline
  • Combination
  • Homocysteine
  • Methionine
  • Methionine dependence
  • Nude mice
  • Recombinant methioninase
  • Rescue
  • Restriction
  • Temozolomide

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Total Methionine Restriction Treatment of Cancer. / Hoffman, Robert M.; Kokkinakis, Demetrius M.; Frenkel, Eugene P.

In: Methods in molecular biology (Clifton, N.J.), Vol. 1866, 01.01.2019, p. 163-171.

Research output: Contribution to journalArticle

Hoffman, Robert M. ; Kokkinakis, Demetrius M. ; Frenkel, Eugene P. / Total Methionine Restriction Treatment of Cancer. In: Methods in molecular biology (Clifton, N.J.). 2019 ; Vol. 1866. pp. 163-171.
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