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[Metallothionein as a resistance factor for antitumor drugs]
1Dept. of Public Health, School of Pharmaceutical Sciences, Kitasato University.
Abstract:
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.
Insights
Metallothionein (MT) may contribute to multi-drug resistance in cancer cells. Overexpressing MT in cultured cells increased resistance to several chemotherapy drugs, suggesting MT
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Context:
- Metallothionein (MT) is a metal-binding protein known to be induced by heavy metals.
- MT has shown potential in mitigating antitumor drug toxicity.
- Conversely, MT induction in tumors can reduce drug efficacy.
Purpose:
- To investigate the role of Metallothionein (MT) in acquired multi-drug resistance in tumor cells.
- To determine if cells overexpressing MT exhibit altered sensitivity to various antitumor agents.
Summary:
- Cadmium-resistant HeLa cells (HeLa-R), with 180 times higher MT levels than HeLa-S cells, were used.
- HeLa-R cells demonstrated significantly increased resistance to cis-diamminedichloroplatinum (cis-DDP), adriamycin (ADR), peplomycin (PEP), and melphalan (MEL).
- No significant differences in radical scavenging factors (excluding MT) or drug uptake were observed between the cell strains.
Impact:
- The findings support the hypothesis that Metallothionein (MT) functions as a multi-drug resistance factor in tumor tissues.
- This research may inform strategies for overcoming drug resistance in cancer therapy.
- Understanding MT's role could lead to novel therapeutic approaches targeting drug-resistant cancers.