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Gamma-Glutamylcysteine synthetase and chemosensitivity

Nishio, K.; Kurokawa, H.; Ishida, T.; Fukuoka, K.; Saijo, N.

Gan to Kagaku Ryoho. Cancer and ChemoTherapy 24(4): 418-423

1997

ISSN/ISBN: 0385-0684
PMID: 9063478
Document Number: 479102
The gene transfectant with gamma-glutamylcysteine synthetase (gamma-GCS) gene, a rate limiting enzyme in GSH biosynthesis, exerted increased GSH content and ATP-dependent glutathione S-conjugate export pump (GS-X pump) decreased intracellular platinum and sensitivity against cisplatin. It is suggested that GS-X pump expression is related to cellular GSH metabolism and involved in cisplatin resistance. gamma-GCS transfectant also showed the resistance to MMC with the decreased DNA-MMC adduct. On the other hand, a MMC derivative, KW-2149, which is activated by thiol molecule, exhibited high cytotoxicity against the transfectant with an equal amount of DNA-MMC adduct compared with parental cells. It is suggested that KW-2149 could circumvent the GSH-mediated drug resistance.

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