Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of a B16 melanoma cell line with 2.45-GHz pulsed microwaves (10 mW/cm2, 10-microseconds pulses at 100 pps, 1-h exposure; SAR, 0.2 W/kg) resulted in changes of membrane ordering as measured by EPR (electron paramagnetic resonance) reporter techniques. The changes reflected a shift from a more fluid-like phase to a more solid (ordered) state of the cell membrane. Exposure of artificially prepared liposomes that were reconstituted with melanin produced similar results. In contrast, neither B16 melanoma cells treated with 5-Bromo-2-Deoxyuridine (3 micrograms/day x 7 days) to render them amelanotic, nor liposomes prepared without melanin, exhibited the microwave-facilitated increase of ordering. Inhibition of the ordering was achieved by the use of superoxide dismutase (SOD), which strongly implicates oxygen radicals as a cause of the membrane changes. The data indicate that a significant, specific alteration of cell-membrane ordering followed microwave exposure. This alteration was unique to melanotic membranes and was due, at least in part, to the generation of oxygen radicals.
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PMID:Modification of membrane fluidity in melanin-containing cells by low-level microwave radiation. 131 76

Clinical and experimental observations suggest that tumor-induced endothelial cell injury may be one of several initial events in the establishment of tumor metastases. To test this hypothesis, the authors have analyzed the interaction of malignant melanoma (ST-ML-12) multicenter tumor spheroids with endothelial cell monolayers in a three-dimensional coculture system. After 1.5 hours of interaction, the authors observed a toxic effect on endothelial cells in the perispheroid region. The latter was demonstrated by testing membrane integrity with the fluorescent probes acridine orange/ethidium bromide and resulted in sensitivity to shear stress of the damaged cells. The endothelium then underwent a regenerative cycle to replace the denuded halo. Addition of the oxygen radical-scavenging enzyme superoxide dismutase to the culture medium prevented this endothelial cell damage in a dose-dependent manner for up to 12 hours. By contrast, catalase, deferoxamine mesylate, allopurinol, and the proteinase inhibitors soybean trypsin inhibitor and aprotinin were not protective under the same conditions. The endothelial damage was dependent on the attachment of the spheroids. Medium conditioned by ST-ML-12-spheroids proved to be ineffective. A similar, but less prominent, deleterious effect was seen when human peritoneal mesothelial cells were used in place of the human umbilical vein endothelial cells. Spheroids of the uroepithelial cell line HU-609 were used as control. No toxicity was observed in these cocultures. Melanin biosynthesis is associated with the production of oxygen-derived free radicals. The results suggest a possible implication of these free radicals in metastasis formation of malignant melanoma.
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PMID:Interaction of human malignant melanoma (ST-ML-12) tumor spheroids with endothelial cell monolayers. Damage to endothelium by oxygen-derived free radicals. 151 67

A B16 melanoma line was repeatedly transplanted subcutaneously in C57BL/6 mice. On day 4 after every transplant, the animals were treated with doxorubicin (DXR), 10 mg/kg i.p. The aim of the work was to develop an in-vivo model of resistance to the antiblastic in order to analyze some possible mechanistic aspects of the process in the course of time. After 16 transplants and treatments the melanoma completely lost its sensitivity to the antiproliferative effects of maximal tolerated doses of DXR and showed over-expression of P-glycoprotein. Compared to the parental line, the in vitro resistance index was 4.6. After 27 transplants and treatments the melanoma did not increase its in vitro resistance to DXR further, and this resistance was completely reversed by verapamil. The behavior of the antioxidant defenses (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, glutathione reductase and glutathione) was evaluated after 4, 16 and 27 transplants and treatments with DXR. At no stage did the treated melanoma show any variation in the antioxidant enzymes. Compared to the parental counterpart its glutathione levels were elevated after four treatments (+80%), when, however, the line was still sensitive to the in vivo effects of DXR, and after 16 treatments (+30%). Instead, no variation of the glutathione content was seen after 27 treatments with DXR. These results seem to exclude the possibility that the antioxidant defenses play a major role in the resistance of this B16 melanoma line to DXR. On the other hand, the low but, however, 'clinically' significant resistance of the tumor to the antiblastic seems mainly related to the mechanisms linked to the P-glycoprotein over-expression.
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PMID:Antioxidant defenses in a B16 melanoma line resistant to doxorubicin: an in vivo study. 168 13

Liposome models of melanosomes (lipo-melanosomes) were used to investigate how phospholipid composition, charge and medium pH may affect the lipo-melanosome membrane permeability to active oxygen species or melanin synthesis intermediaries. Active oxygen accumulated only at pH 6.4 and was polarographically monitored using superoxide dismutase and/or catalase. Cholesterol appears to increase the O2- accumulation at pH 6.4 while incorporation of positive phospholipids within lipo-melanosomes results in the loss of latency with respect to tyrosinase substrate and intermediates of melanin synthesis.
Melanoma Res
PMID:Changes of lipo-melanosome membrane leakage versus pH, charge and composition. 184 15

Human melanoma cells were grown to exponential and stationary phases showing melanin contents of 4.2 +/- 0.3 and 11.3 +/- 0.6 micrograms/10(6) cells, respectively. The cells were separated in four subpopulations by a Percoll gradient; the subpopulation of density 1.07 (g/ml) was the most enriched in pigmented cells and produced 28 and 58% of the cells in exponential and stationary phases, respectively. Melanoma cells had similar superoxide dismutase and glutathione peroxidase activities in exponential and stationary phases. Moreover melanoma cells exhibited a higher catalase activity in the stationary phase: whole homogenate and cytosol activities were 7.0 +/- 0.3 and 10.8 +/- 0.6 U/mg protein, whereas in exponential phase the activities were 4.9 +/- 0.1 and 7.6 +/- 0.3 U/mg protein for whole homogenate and cytosol, respectively. The intracellular H2O2 steady-state concentration was 3.3 +/- 0.2 and 2.1 +/- 0.2 microM H2O2 for exponential and stationary phases, respectively. The spontaneous chemiluminescence of the two culture phases was 169 +/- 27 cps/10(6) cells (exponential) and 78 +/- 24 cps/10(6) cells (stationary). The cytotoxicity of H2O2 generated extracellularly by glucose oxidase was determined after 60 min of exposure. IC50 values for exponential and stationary cell cultures were 0.9 and 2.4 mU/ml of glucose oxidase, respectively. The increased catalase activities in the stationary phase as compared with the exponential phase are consistent with the decreased intracellular H2O2, with the decreased spontaneous chemiluminescence, and with the increased resistance to exogenous H2O2.
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PMID:Melanin content and hydroperoxide metabolism in human melanoma cells. 189 32

Melanin contains melanin-free radicals and can both absorb and produce additional free radicals and active oxygen species on exposure to various stimuli. Yet its role in the radiation responses of malignant melanoma has been little studied. In this report, three subclones of Cloudman S91 mouse melanoma clone PC1A varying in constitutive melanin content were compared with respect to killing by gamma irradiation. Radiation responses correlated with melanin content. The least melanotic line, S91/amel, was most sensitive and the most melanotic line, S91/I3, was most resistant. Curve fitting using the linear-quadratic model suggests that S91/amel is killed only by single event inactivations; S91/I3, only by double event inactivations; and S91/M1B, with intermediate melanin and radiation response, by both types of inactivations. Split dose experiments confirmed a lack of immediate split dose recovery in S91/amel and its existence in S91/I3. Potentially lethal damage and its repair could be demonstrated in both S91/amel and S91/I3. Double strand break (DSB) induction was evaluated as a function of gamma ray dose in DNA of S91/I3 and S91/amel, as well as in EMT6, a mouse mammary cancer line that lacks tyrosinase and melanin. The rates of induction were proportional to cellular melanization, i.e., the rate of DSB induction was greatest in S91/I3, least in EMT6. Levels of thioredoxin reductase (TR), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) were determined in S91/amel and S91/I3. TR was the same in both cell lines, while the other three enzymes were 3- to 4-fold lower in S91/amel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does melanin affect the low LET radiation response of Cloudman S91 mouse melanoma cell lines? 194 13

Superoxide dismutases (SOD), which are enzymes scavenging the superoxide radical, were studied in two variant lines of the B16 melanoma: B16F1 with low metastatic potential and B16F10 with high metastatic potential. SOD activity was measured by a method utilizing reduction in the chemiluminescence of luminol. Using cell free extracts it was shown that the highly metastatic B16F10 cell line has a SOD activity lower (20.70 +/- 3.07) units/mg protein, n = 8, than that of the less metastatic B16F1 cell line (81.38 +/- 6.78) units/mg protein, n = 8. Acrylamide gel electrophoresis suggested that Mn-SOD activity is higher in B16F1 cells.
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PMID:Lowered superoxide dismutase in highly metastatic B16 melanoma cells. 203 8

Kinetic experiments are reported showing that mammalian tyrosinase from B16 mouse melanoma is significantly activated by catalytic amounts of ferrous ions. Monitoring of tyrosine oxidation by both dopachrome formation and oxygen consumption showed that ferrous ions at micromolar concentrations induce a marked enzymatic activity with 0.01 U/ml of highly purified tyrosinase, whereas no detectable reaction occurs in the absence of metal over a sufficiently prolonged period of time. The extent of the activating effect, which is specific for the reduced form of iron, is proportional to the concentration of the added metal with a typical saturation profile, no further effect being observed beyond a threshold value. Changing the buffer system from phosphate to hepes or tris results in a marked decrease of the Fe2(+)-induced activation. Scavengers of active oxygen species, such as superoxide dismutase, catalase, formate and mannitol have no detectable effect on the tyrosinase activity. These results are accounted for in terms of an activation mechanism involving reduction of the cupric ions at the active site of the resting enzyme.
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PMID:Activation of mammalian tyrosinase by ferrous ions. 210 73

The effect of zinc ions on B16 mouse melanoma lines, HeLa cells and I-221 epithelial cells was investigated in vitro in order to ascertain whether sensitivity to Zn2+ is a general feature of cells in vitro and in an attempt to elucidate the mechanism(s) of zinc cytotoxicity. The proliferation of B16, HeLa and I-221 cell lines was inhibited by 1.25 x 10(-4), 1.50 x 10(-4) and 1.50 x 10(-4) mol/l Zn2+, respectively. The free radical scavengers, methimazole and ethanol, did not suppress the toxicity of Zn2+, neither did superoxide dismutase or catalase. The addition of the chelating agent EDTA reduced the zinc cytotoxicity. It was possible to suppress the cytotoxicity of zinc by increasing the concentration of either Fe2+ or Ca2+ but not Mg2+, which suggests that a prerequisite for the toxic action of zinc is entry into cells using channels that are shared with iron or calcium. This view was supported by experiments in which transferrin intensified the cytotoxic action of zinc in serum-free medium. Another agent facilitating zinc transport, prostaglandin E2, inhibited the proliferation of the B16 melanoma cell line. There were no conspicuous differences in zinc toxicity to pigmented and unpigmented cells. The toxic effect of zinc in the cell systems studied exceeded that of iron, copper, manganese and cobalt in the same concentration range. In vitro, Zn2+ should be regarded as a dangerous cation.
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PMID:Cytotoxicity of zinc in vitro. 270 7

Two melanotic human melanoma cell lines, IRE 1 and IRE 2, and the lymphoma- and leukaemia-derived cell lines Raji and K 562, were exposed to different concentrations (from 5 X 10(-3) M to 10(-5) M) of phenols, both substrates (s) and non-substrates (ns) of tyrosinase, in the presence or absence of the oxygen-radical-scavenger enzymes superoxide dismutase, catalase and peroxidase. Monophenols were tyrosine (s), 4-hydroxyanisole (s) and butylated hydroxyanisole (ns); diphenols were L-3,4-dihydroxyphenylalanine (s), dopamine (3,4-dihydroxyphenethylamine) (s), terbutylcatechol (s), hydroquinone (s) and resorcinol (ns); triphenols were 6-hydroxydopa (3,4,6-trihydroxyphenylalanine) (s) and methyl gallate (s). Triphenols and o- and p-diphenols underwent complete oxidation in culture medium within 24 h of incubation and were significantly more toxic than monophenols and the m-diphenol resorcinol, which, under the same cultural conditions, were much more stable. No significant differences in percentage survival were found among the different cell lines for each drug tested. The major component of toxicity up to 24 h of di- and tri-phenols is due to toxic oxygen species acting outside the cells and not to cellular uptake of these phenols as such. In fact the addition of oxygen-radical-scavenger enzymes significantly (P less than 0.01) decreased the adverse effect of these drugs on all cell lines. The lower toxicity of monophenols and resorcinol as compared with that of di- and tri-phenols is due, in our opinion, to the fact that they are less oxidized under the conditions existing in the culture medium, and therefore do not produce sufficient levels of oxygen radicals. For these compounds, a primary intracellular action has to be taken into account to explain their cytotoxicity.
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PMID:Comparative cytotoxicity of phenols in vitro. 282 25


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