Intracellular sequestration of anti-tumor drugs by metallothionein
| Autor: | T, He, D, Wei, D, Fabris, C, Fenselau |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Alkylation
Cell Survival Antineoplastic Agents Methylation Mass Spectrometry Cadmium Chloride Urinary Bladder Neoplasms Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Tumor Cells Cultured Animals Humans Protein Isoforms Metallothionein Trypsin Rabbits Chromatography High Pressure Liquid |
| Zdroj: | Cellular and molecular biology (Noisy-le-Grand, France). 46(2) |
| ISSN: | 0145-5680 |
| Popis: | Acquired drug resistance is one of the most important problems in cancer chemotherapy. One of the mechanisms proposed to contribute to this phenomenon is the sequestration of alkylating agents by metallothionein (MT) in vivo. In this study cadmium-induced human bladder tumor T24 cells were exposed to the therapeutic agents chlorambucil and melphalan. MT-2a, was shown by capillary electrophoresis to comprise 56% of the MT isoforms in induced cells, and drug adducts of MT-2a were isolated and characterized by HPLC and electrospray ionization mass spectrometry. One to four equivalents of drug were found to be covalently adducted. Major binding sites on metallothionein were located in the C-terminal domain by peptide mapping, consistent with previous studies in vitro. |
| Databáze: | OpenAIRE |
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