GSH, GSH-related enzymes and GS-X pump in relation to sensitivity of human tumor cell lines to chlorambucil and adriamycin.
Glutathione (GSH) contents and activities of glutathione S-transferase (GST), glutathione reductase (GSH-RD), glutathione peroxidase (GSHpx) and glutathione conjugate export pump (GS-X pump) were determined in eight human tumor cell lines with different sensitivities to adriamycin and chlorambucil. Correlations between sensitivities of the human tumor cells to adriamycin and chlorambucil and the glutathione related factors were analyzed statistically. Sensitivities of the human tumor cells to chlorambucil were found to be correlated to all the glutathione related factors tested (r=0.68-0.88). IC50 values of adriamycin were also positively correlated to GSH contents and activities of GSH-RD, GSHpx and GS-X pump with r values ranging from 0.66 to 0.77 but not to GST activity (r=0.25). Chang liver cells with highest GSH content and highest activities of GST, GSH-RD, GSHpx and GS-X pump were most resistant to both adriamycin and chlorambucil. These data suggested that glutathione related factors may work as an overall detoxification system participating in the detoxification of anticancer drugs such as adriamycin and chlorambucil, and to be involved in cellular resistance to these drugs.
Zhang
K
K
Department of Experimental Surgery, BLK 9, Level 2, Singapore General Hospital, Singapore 169608, Singapore.
Yang
E B
EB
Wong
K P
KP
Mack
P
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002699:Chlorambucil / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C086860:glutathione transporter; D002699:Chlorambucil; D004317:Doxorubicin; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione