TY - JOUR
T1 - The close association of π-class glutathione S-transferase with drug sensitivity to alkylating agents and cisplatin in human cancer cells
AU - Tanaka, Toshiya
AU - Yokomizo, Akira
AU - Uchiumi, Takeshi
AU - Furukawa, Manabu
AU - Wada, Morimasa
AU - Kuwano, Michihiko
PY - 1997
Y1 - 1997
N2 - Buthionine sulfoximine (BSO) is a synthetic amino acid that irreversibly inhibits glutathione biosynthesis. A BSO-resistant line, KB/BSO3, was established from human epidermoid cancer KB cells; and other BSO-resistant lines, HLE/BSO1 and HLE/BSO2, were from human hepatic cancer HLE cells. Cellular level of π-class glutathione S-transferase (GSTP1) in KB/BSO3 was less than 10% of the parental KB, and those in HLE/BSO1 and HLE/BSO2 was 30-40% of the parental HLE cells. KB/BSO3, HLE/BSO1 and HLE/BSO2 had collateral sensitivities to a potent anticancer agent, cisplatin, and alkylating agents including melphalan and nitrosourea. The GSTP1 cDNA transfectant KB/BSO3-π established from KB/BSO3, and also HLE/BSO1-π and HLE/BSO2-π established from HLE/BSO1 and HLE/BSO2, restored cellular sensitivities to cisplatin and alkylating agents to similar levels as KB and HLE cells. Our present results indicate that GSTP1 levels apparently limit cellular sensitivities to cisplatin and alkylating agents, suggesting that GSTP1 is a useful diagnostic marker for drug sensitivities to these agents in human cancer cells.
AB - Buthionine sulfoximine (BSO) is a synthetic amino acid that irreversibly inhibits glutathione biosynthesis. A BSO-resistant line, KB/BSO3, was established from human epidermoid cancer KB cells; and other BSO-resistant lines, HLE/BSO1 and HLE/BSO2, were from human hepatic cancer HLE cells. Cellular level of π-class glutathione S-transferase (GSTP1) in KB/BSO3 was less than 10% of the parental KB, and those in HLE/BSO1 and HLE/BSO2 was 30-40% of the parental HLE cells. KB/BSO3, HLE/BSO1 and HLE/BSO2 had collateral sensitivities to a potent anticancer agent, cisplatin, and alkylating agents including melphalan and nitrosourea. The GSTP1 cDNA transfectant KB/BSO3-π established from KB/BSO3, and also HLE/BSO1-π and HLE/BSO2-π established from HLE/BSO1 and HLE/BSO2, restored cellular sensitivities to cisplatin and alkylating agents to similar levels as KB and HLE cells. Our present results indicate that GSTP1 levels apparently limit cellular sensitivities to cisplatin and alkylating agents, suggesting that GSTP1 is a useful diagnostic marker for drug sensitivities to these agents in human cancer cells.
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M3 - Article
C2 - 21533477
AN - SCOPUS:0030961699
VL - 10
SP - 1009
EP - 1014
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 5
ER -