Pathological Metabolism of Methionine in Malignant Cells Is a Potential Target for the Antitumor Therapy

VS Pokrovskii1, DZh Davydov1, NV Anufrieva2, DD Zhdanov3, EM Treshchalina1, TV Demidkina2, EA Morozova2

1 NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 VA Engelhardt Institute of Molecular Biology, 32 Vavilova str., Moscow, Russian Federation, 119991

3 VN Orekhovich Institute of Biomedical Chemistry, 10 bld. 8 Pogodinskaya str., Moscow, Russian Federation, 119121

For correspondence: Vadim Sergeevich Pokrovskii, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: 8(499)324-14-09; e-mail: vadimpokrovsky@yandex.ru

For citation: Pokrovskii VS, Davydov DZh, Anufrieva NV, et al. Pathological Metabolism of Methionine in Malignant Cells Is a Potential Target for the Antitumor Therapy. Clinical oncohematology. 2017;10(3):324–32 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-324-332


ABSTRACT

This review presents the characteristics of the cellular metabolism of methionine, as well as known data on the mechanisms of the development of methionine dependence in malignant cells. The possibilities of using a non-methionine diet for the control of the tumor growth in patients with various forms of cancer are considered. The newest information about methionine-γ-lyase, an enzyme providing elimination of methionine from plasma, is grouped and summarised. Its role as a potential antitumor enzyme is disclosed. Data on methionine-γ-lyase producers, activity of this enzyme, obtained from various sources, and information on tumor models and cell cultures, showing methionine dependence are summarised.

Keywords: methionine-γ-liase, methionine, methionine dependency, cancer cells, cancer, anticancer enzymes, antitumor therapy.

Received: December 16, 2016

Accepted: March 6, 2017

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Enzymes in oncohematology: relevant directions of experimental studies and prospects of clinical use

V.S. Pokrovskiy and H.M. Treshchalina

N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation


ABSTRACT

Recently, the field of development of the novel enzyme-based drugs showed remarkable advances. In addition to L-asparaginase which have been already used in oncohematology for more than 30 years, the two new enzymes, L-arginine deiminase and ranpirnase, underwent the several phases of clinical trials. Anticancer activity in vivo at the preclinical stage was shown for a number of enzymes: L-methionine-gamma-lyase, L-lysine-alpha-oxydase, and binase. This review discusses the enzymes which possess anticancer activity and prospects for their use in oncohematology.


Keywords: anticancer enzymes, L-asparaginase, L-methionine gamma-lyase, L-lysine alpha-oxydase, L-arginine deiminase, L-phenylalanine ammonia-lyase, ranpirnase.

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