Autor: |
Walker, P Roy, Smith, Brandon, Carson, Christine, LeBlanc, Julie, Sikorska, Marianna, Woodhouse, Clive S, Morgan, A Charles |
Předmět: |
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Zdroj: |
Cell Death & Differentiation; Apr97, Vol. 4 Issue 3, p233, 9p |
Abstrakt: |
Methionine synthase, a critical enzyme in deoxyribonucleotide biosynthesis for DNA replication, requires vitamin B[sub 12] as a cofactor. We have tested the hypothesis that depletion of cells of vitamin B[sub 12] would block growth of neoplastic cells and divert them into apoptosis and could form the basis of a new therapeutic strategy for cancer treatment. Using nitrous oxide to inactivate vitamin B[sub 12] we show that, in a variety of cell lines in vitro, methionine synthase is rapidly inhibited, the cells cease proliferation and undergo apoptosis. The kinetics of cell death, once started, are similar to those observed following methotrexate treatment or serum withdrawal. This is the first observation of apoptosis being induced following depletion of an essential metabolite as opposed to the more conventional strategy of adding a toxic drug to damage cells thereby triggering apoptosis. Moreover, vitamin B[sub 12] depletion has no effect on the non-proliferating cell population. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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