[Metallothionein as a resistance factor for antitumor drugs].
Metallothionein (MT), a metal binding protein induced by bismuth and other heavy metals, has been proved to have a potential to prevent toxic side effects of several antitumor drugs. It has also been demonstrated that the induction of MT in tumor tissues diminishes the antitumor activity of the drugs as well. These facts suggest a possibility that MT may play an important role in acquiring multi-drug-resistance in tumor cells. Thus, we were encouraged to examine the sensitivity of cultured cells overexpressing MT to various antitumor drugs which differ from each other in the mechanism of action. Cadmium-resistant cells (HeLa-R) were obtained from HeLa S3 cells (HeLa-S) by successive cultivation in a medium containing 100 microM CdCl2. MT level in HeLa-R was 180 times higher than that of HeLa-S. Comparison of the sensitivity of these two strains to the antitumor drugs, such as, cis-diamminedichloroplatinum (cis-DDP), adriamycin (ADR), peplomycin (PEP) and melphalan (MEL), revealed that HeLa-R was significantly more resistant to these drugs than HeLa-S. Further, there was no significant discrepancy between these strains, either in the level of major radical scavenging factors other than MT or in the cellular uptake of the drugs. The experimental results described above appear to support the hypothesis that MT may act as a multi-drug-resistance factor in tumor tissues.
Imura
N
N
Dept. of Public Health, School of Pharmaceutical Sciences, Kitasato University.
Naganuma
A
A
Satoh
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology; D004351:Drug Resistance; D006367:HeLa Cells; D006321:Heart / Q000187:drug effects; D006801:Humans; D008658:Inactivation, Metabolic; D008668:Metallothionein / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D004317:Doxorubicin; D008668:Metallothionein