Glutamine antagonists work as anticancer agents:
A. By inhibiting purine nucleotide synthesis
B. By blocking formation of AMP from IMP
C. By inhibiting amidotransferase that transfers amide of glutamine to an acceptor molecule
D. By inhibiting PRPP synthetase
Ans.
C. Inhibiting
amidotransferases 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 Ca÷2 dependent and results from decreased cell division and increased cell death.
4. Glutamate antagonists produce:
a. Morphological alterations in tumor cells,
b. Reduced membrane ruffling and pseudopodial protrusions,
c. Decrease their motility and invasive growth.
d. Ethance in vitro cytostatic and cytotoxic effects of common chemotherapeutic agents used in cancer therapy.
e. 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. Other mechanism of minor importance are also present.
Riluzole is a glutamate inhibitor which is used for treatment of ALS (Amyotrophic Lateral sclerosis)
Side effects are: Dizziness, Weight loss, Elevated liver enzymes, Skeletal weakness.
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 Ca÷2 dependent and results from decreased cell division and increased cell death.
4. Glutamate antagonists produce:
a. Morphological alterations in tumor cells,
b. Reduced membrane ruffling and pseudopodial protrusions,
c. Decrease their motility and invasive growth.
d. Ethance in vitro cytostatic and cytotoxic effects of common chemotherapeutic agents used in cancer therapy.
e. 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. Other mechanism of minor importance are also present.
Riluzole is a glutamate inhibitor which is used for treatment of ALS (Amyotrophic Lateral sclerosis)
Side effects are: Dizziness, Weight loss, Elevated liver enzymes, Skeletal weakness.
