Toxicity of enzymatic oxidation products of spermine to human melanoma cells (M14): sensitisation by heat and MDL 72527
| Autor: | Maria Condello, Nikolaus Seiler, Laura Dalla Vedova, Francesca Belli, Paola Palmigiani, Manuela Marra, Agnese Molinari, Enzo Agostinelli, Giuseppe Arancia |
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| Rok vydání: | 2006 |
| Předmět: |
Amine oxidase
Hot Temperature Time Factors Melanoma cell Cell Survival Spermine Vacuole CHO Cells Biology chemistry.chemical_compound Cell Line Tumor Cricetinae Putrescine Animals Humans Hyperthermia Viability assay Annexin A5 Hydrogen peroxide Cytotoxicity Melanoma Monoamine Oxidase Molecular Biology Dose-Response Relationship Drug Molecular Structure Bovine serum amine oxidase MDL 72527 Cell Biology Flow Cytometry Microscopy Electron chemistry Biochemistry Apoptosis Cell culture Doxorubicin Drug Resistance Neoplasm Reactive Oxygen Species Oxidation-Reduction |
| Popis: | In situ formation of cytotoxic metabolites by an enzyme-catalyzed reaction is a recent approach in cancer chemotherapy. We demonstrate that multidrug resistant human melanoma cells (M14 ADR) are more sensitive than the corresponding wild type cells (M14 WT) to hydrogen peroxide and aldehydes, the products of bovine serum amine oxidase (BSAO)-catalyzed oxidation of spermine. Hydrogen peroxide was mainly responsible for the loss of cell viability. With about 20%, the aldehydes formed from spermine contribute also to cytotoxicity. Elevation of temperature from 37 degrees C to 42 degrees C decreased survival of both cell lines by about one log unit. Pre-treatment with N1,N4-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527), a lysosomotropic compound, sensitized cells to toxic spermine metabolites. MDL 72527 (at 300 microM) produced in M14 cells numerous cytoplasmic vacuoles which, however, disappeared by 24 h, even in the presence of the drug. Mitochondrial damage, as observed by transmission electron microscopy, correlated better with the cytotoxic effects of the treatment than vacuole formation. Since the release of lysosomal enzymes causes oxidative stress and apoptosis, we suggest that the lysosomotropic effect of MDL 72527 is the major reason for its sensitizing effect. |
| Databáze: | OpenAIRE |
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