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3 results on '"H Alvero-Jackson"'

1. Relationship between melanogenesis, glutathione levels and melphalan toxicity in human melanoma cells

Author

A M Mooy, H Alvero-Jackson, Messod Benathan, C. Scaletta, and E. Frenk

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
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.

Published
1992

2. Malignant melanoma, follow-up 1975–1991

Author

L. Alvero, E. Frenk, and H. Alvero-Jackson

Subjects
Cancer Research, Oncology, business.industry, Melanoma, Cancer research, Medicine, Dermatology, business, medicine.disease, Malignant transformation
Published
1993

3. Relationship between melanogenesis, glutathione levels and melphalan toxicity in human melanoma cells.

Author

Benathan M, Alvero-Jackson H, Mooy AM, Scaletta C, and Frenk E

Subjects
Bucladesine pharmacology, Buthionine Sulfoximine, Cell Differentiation drug effects, Cell Division drug effects, Cell Survival drug effects, Dose-Response Relationship, Drug, Eye Neoplasms pathology, Humans, Kinetics, Melanoma pathology, Melanoma ultrastructure, Methionine Sulfoximine analogs & derivatives, Methionine Sulfoximine pharmacology, Microscopy, Electron, Neoplasm Staging, Skin Neoplasms pathology, Tumor Cells, Cultured, Eye Neoplasms metabolism, Glutathione metabolism, Glutathione Transferase metabolism, Melanins biosynthesis, Melanoma metabolism, Melphalan pharmacology, Monophenol Monooxygenase metabolism, Skin Neoplasms metabolism
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.

Published
1992
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