Methionine dependence of tumor cells: programmed cell survival?

Abstract:

:A majority of tumor cell lines are considered to be "methionine-dependent" because of their inability to grow in culture when methionine is replaced by its precursor, homocysteine. We have previously shown that this phenotype is not due to the incapacity to synthesize methionine from homocysteine but rather to a deficiency in the "methionine salvage pathway", including 4-methylthio-2-oxobutanoic acid (MTOB), which is transaminated into methionine. At low concentrations MTOB can restore normal growth of methionine-dependent cell lines in the absence of methionine. However, when MTOB concentrations are increased the cells undergo apoptosis. Methional, a metabolite of MTOB produced by the branched-chain oxo acid dehydrogenase complex, is a potent inducer of apoptosis in a murine lymphoid cell line. We suggest that the methionine-dependent phenotype is associated with a reduced content of methional, which behaves as a proapoptotic agent. For this reason, methionine-dependent cells have a relative survival advantage.

journal_name

Oncol Res

journal_title

Oncology research

authors

Dumontet C,Roch AM,Quash G

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

469-71

issue

12

eissn

0965-0407

issn

1555-3906

journal_volume

8

pub_type

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