Back to Search
Start Over
Relationship between melanogenesis, glutathione levels and melphalan toxicity in human melanoma cells
- Source :
- Melanoma Research. 2:305-314
- Publication Year :
- 1992
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 1992.
-
Abstract
- Resistance to alkylating agents has been correlated with cellular levels of reduced glutathione (GSH) and glutathione-S-transferase (GST). GSH is also involved in regulation of melanin synthesis. Therefore, we examined sensitivity to melphalan as a function of differentiation and GSH/GST levels in three human melanoma cell lines. The Me8 cell line, classified as undifferentiated on the basis of cell shape, absence of pigment, insignificant dopa oxidase activity and presence of inhibitors of dopa-melanin formation, showed the lowest GST activity among the cell lines investigated. GLL19 cells exhibited normal differentiation as indicated by the presence of dendrites, typical eumelanosomes, melanin granules and dopa oxidase activity. These cells showed the highest GSH content and the highest GST activity. The JUSO cell line showed incomplete differentiation, and its dopa oxidase and GST activities were intermediate between the Me8 and GLL19 cell lines. The sensitivity of melanoma cell lines to melphalan increased with their degree of differentiation; it was lowest for Me8, intermediate for JUSO and highest for GLL19. Dibutyryl cyclic AMP (dbcAMP) enhanced melphalan toxicity against Me8 cells. Depletion of intracellular GSH with buthionine sulphoximine (BSO) resulted in a three-fold increase in melphalan sensitivity in all three cell lines. Our results indicate that melphalan toxicity is related to cell differentiation and GSH status of melanoma cells. Based on the observed relationship between dopa oxidase, GSH/GST levels and drug toxicity, it is proposed that competition for the GSH pool between quinonoid melanin intermediates and melphalan could diminish drug conjugation and increase cytotoxicity.
- Subjects :
- Melphalan
Cancer Research
Skin Neoplasms
Cell Survival
Cellular differentiation
Dermatology
Melanin
chemistry.chemical_compound
Methionine Sulfoximine
Tumor Cells, Cultured
medicine
Humans
Buthionine sulfoximine
Buthionine Sulfoximine
Melanoma
Glutathione Transferase
Neoplasm Staging
Melanins
Dose-Response Relationship, Drug
Monophenol Monooxygenase
Eye Neoplasms
Cell Differentiation
Glutathione
Molecular biology
Kinetics
Microscopy, Electron
Bucladesine
Oncology
chemistry
Cell culture
Toxicity
Cell Division
Intracellular
medicine.drug
Subjects
Details
- ISSN :
- 09608931
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- Melanoma Research
- Accession number :
- edsair.doi.dedup.....d9182136ae7e38c3875d2793b84b1c2d