Imbalance in the Antioxidant Pool in Melanoma Cells and Normal Melanocytes from Patients with Melanoma

Abstract

In order to evaluate the free radical defense systems of melanocytes and their possible correlation with melanoma, we have studied in cultured normal human melanocytes (20), normal melanocytes from melanoma patients (15), and melanoma cells (40) the fatty acid pattern of membrane phospholipids as a target of peroxidative damage and the superoxide dismutase and catalase activities, vitamin E, and ubiquinone levels as intracellular antioxidants. Cells were cultured in the same medium and analyzed at III or IV passage. Compared to the values obtained in normal human melanocytes, melanoma cells showed on average: a) higher levels of polyunsaturated fatty acids, b) increased superoxide dismutase and decreased catalase activities, higher vitamin E, and lower ubiquinone levels. Among the normal melanocytes from melanoma patients studied, two groups were differentiated: a) cultures (7) with enzymatic and non-enzymatic antioxidants level similar to those of normal human melanocytes; b) cultures (8) with antioxidant patterns similar to those observed in melanoma cells. Polyunsaturated fatty acids were also increased in the latter group. The results indicate that in melanoma cells and in a percentage of normal melanocytes from melanoma patients, an imbalance in the antioxidant system can be detected that can lead to endogenous generation of reactive oxygen species and to cellular incapability of coping with exogenous peroxidative attacks. These alterations could be correlated with the malignant transformation of cells and with the progression of the disease.

Systematic review of studies investigating the association between dietary habits and cutaneous malignant melanoma

“…In fact, Meyskens et al [68] have hypothesized that CMM pathogenesis encompasses the early oxidation of melanin to the pro-oxidant quinone-imine which may play a role in accumulation of metals and other chemicals. This process is contrasted by cellular antioxidants whose depletion is indeed considered a feature of CMM pathogenesis [69,70].…”

Redox Regulation in Human Melanocytes and Melanoma

“…Although abnormalities in chromosome 6 and the MnSOD gene have been demonstrated in some melanomas (57), this is uncommon and unlikely to provide a genetic or generic basis for the altered anti-oxidant phenotype. Picardo and his colleagues have followed up this observation and found that the anti-oxidant phenotype of normal epidermal melanocytes from patients with melanoma fell into one of two categories: a) the same as melanocytes from normal donors or b) a phenotype resembling melanoma cells: elevated vitamin E and polyunsaturated fatty acids and a lowered catalase and unchanged SOD activity (58)(59)(60). Remarkably, a similar anti-oxidant pattern was also seen when uveal melanocytes and uveal melanoma cell cultures were compared (61).…”

UVB-induced activation and internalization of keratinocyte growth factor receptor

“…The results were obtained after time integration of the chromatogram and final processing of areas. The identity of each fatty acid has been determined by comparing the mass spectrum of the peaks with those obtained using reference standards (Picardo et al, 1996). Results are the mean7s.d.…”

“…The solvent was evaporated to dryness under a nitrogen stream. Tocopherols, derivatized with N,O-bis-(trimethylsilyl)-trifluoroacetamide (BSTFA) with 1% trimethyl chlorosilane as catalyst, were analysed by GC-MS on SPB1 column (30 m  0.2 mm ID  0.25 mm, Supelchem) by a selected ion (s) monitoring (SIM) technique (Picardo et al, 1996). Results are reported as mean7s.d.…”