Glutamine antagonists work as anticancer agents by:
A. Inhibiting purine nucleotide synthesis
B. Blocking formation of AMP from IMP
C. Inhibiting amido-transferase that transfers amide of glutamine to an acceptor molecule
D. Inhibiting PRPP synthetase
ANS. C.
Inhibitingamido-transferases that transfer amide of glutamine to an acceptor
molecule.
1. The excitatory neurotransmitter glutamate, which regulates proliferation and
migration of neuronal progenitors and immature neurons during the development
of the mammalian nervous system, is present in peripheral cancers.
2. Since both neuronal progenitors and tumor cells possess propensity to proliferate
and to migrate, and since glutamate and glutamate receptors are known to modify
these phenomena in the nervous system it was found and recently reported that
glutamate N-methyl- -aspartate NMDA. and
aamino-3-hydroxy-5-methyl-4-isoxazole-propionate AMPA. antagonists inhibit the proliferation of human
colon adenocarcinoma, astrocytonia, breast and lung carcinoma, and
neuroblastoma cells in vitro.
3. The antiproliferative effect of glutamate antagonists is Ca2+
dependent and results from decreased cell division and increased cell death.
4. Glutamate antagonists produce:
a. Morphological alterations in tumor cells, which consist of
b. Reduced membrane ruffling and pseudopodial protrusions,
c. Decrease their motility and invasive growth.
d. These findings demonstrate the anticancer potential of glutamate antagonists
and suggest that they may be used as an adjunctive measure in the treatment of
cancer.
f. These actions are a consequence of inhibiting amidotransferases that
transfer amide of glutamine to an acceptor molecule.
Riluzole is a glutamate inhibitor. Used for
treatment of ALS Amyotrophic Lateral sclerosis.
Side effects: Dizziness, Weight loss, Elevated
liver enzymes, Skeletal muscle weakness.
