Modulation of resistance to anticancer drugs by inhibition of metallothionein synthesis.
The expression of metallothionein (MT) in certain tumor cells has been associated with resistance to anticancer drugs. In the present study, we examined the effects of inhibition of MT synthesis on resistance to anticancer drugs of human bladder tumor which were inoculated in nude mice. The results show that pretreatment of tumor-bearing mice with zinc salts increased MT content, both in normal and tumor tissues, with a marked reduction in the antitumor activity of cisplatin, Adriamycin, and melphalan. Injection of propargylglycine, an inhibitor of cystathionase, decreased MT induction by zinc in the tumor and diminished the resistance to these drugs. These results suggest a role for MT in drug resistance in tumors, and injection of propargylglycine may provide a potential means to overcome drug resistance caused by elevation of MT levels in certain tumors.
Satoh
M
M
Department of Public Health and Environmental Medicine, Jikei University School of Medicine, Tokyo, Japan.
Cherian
M G
MG
Imura
N
N
Shimizu
H
H
D000480:Alkynes; D000818:Animals; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008558:Melphalan / Q000494:pharmacology; D008668:Metallothionein / Q000096:biosynthesis* / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D010293:Pargyline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013431:Sulfates / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017967:Zinc Compounds / Q000494:pharmacology; D019287:Zinc Sulfate
D000480:Alkynes; D013431:Sulfates; D017967:Zinc Compounds; C009055:propargylglycine; D019287:Zinc Sulfate; D004317:Doxorubicin; D008668:Metallothionein; D010293:Pargyline; D003545:Cysteine; D002945:Cisplatin; D008558:Melphalan; D005998:Glycine