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.
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Hoffman, R.M., Kokkinakis, D.M., Frenkel, E.P. (2019). Total Methionine Restriction Treatment of Cancer. In: Hoffman, R. (eds) Methionine Dependence of Cancer and Aging. Methods in Molecular Biology, vol 1866. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8796-2_13
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DOI: https://doi.org/10.1007/978-1-4939-8796-2_13
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