Total Methionine Restriction Treatment of Cancer

  • Robert M. HoffmanEmail author
  • Demetrius M. Kokkinakis
  • Eugene P. Frenkel
Part of the Methods in Molecular Biology book series (MIMB, volume 1866)


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.

Key words

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


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Robert M. Hoffman
    • 1
    • 2
    Email author
  • Demetrius M. Kokkinakis
    • 3
  • Eugene P. Frenkel
    • 4
  1. 1.AntiCancer, Inc.San DiegoUSA
  2. 2.Department of SurgeryUniversity of CaliforniaSan DiegoUSA
  3. 3.Department of Pathology and the Cancer InstituteUniversity of PittsburghPittsburghUSA
  4. 4.Department of Internal Medicine, Division of Hematology/OncologyUniversity of Texas at Dallas, Southwestern Medical SchoolDallasUSA

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