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)

Ultraviolet-A (UV-A, 320 to 400 nm) radiation comprises 95% of the solar ultraviolet radiation (UVR) reaching the earth's surface. It has been associated experimentally and epidemiologically with malignant melanoma. In this study we investigated whether UV-A radiation can induce a persistent, heritable hypermutability in mammalian cells similar to that observed following ionising radiation (IR). Using the immortalized human skin keratinocyte cell line HaCaT we found that UV-A radiation does lead to a continuing reduction in plating efficiency, an increased "spontaneous" mutant fraction, and an increase in micronucleus formation up to 21 d after initial exposure. Reversal of these effects using catalase may indicate a role for hydrogen peroxide in this phenomenon. These results add to the significance of UV-A radiation as a risk factor in skin carcinogenesis.
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PMID:UV-A induces persistent genomic instability in human keratinocytes through an oxidative stress mechanism. 1186 87

Tetrahydroisoquinolines (TIQs) are endogenous alkaloid compounds detected in urine, central nervous system and some peripheral tissues in Mammalia. No data are at present available on TIQ levels in skin, although in vitro biochemical evidences indicate that they may undergo auto-oxidation with production of reactive oxygen species or may be enzymatically converted into melanin pigments. The effect of two catechol-bearing TIQs, salsolinol (SAL) and tetrahydropapaveroline (THP), on the viability of melanotic or amelanotic melanoma cell lines was investigated. Both SAL and THP were well tolerated up to roughly 30 microM and became overtly toxic at higher concentrations, with SAL being better tolerated than THP. Intracellular activity of some antioxidant enzymes, tyrosinase and alpha-ketoglutarate dehydrogenase was also evaluated to assess the cell response to oxidative and metabolic challenge of TIQs treatment. Catalase and superoxide dismutase pre-treatment only partially prevented TIQs toxicity while a complete protection was obtained with N-acetylcysteine and GSH. TIQs were able to provoke upregulation of the scavenging enzymes catalase and DT-diaphorase and to determine a decrease of the alpha-ketoglutarate dehydrogenase activity. SAL and THP enhanced tyrosinase activity and melanin production, suggesting that they were indeed tyrosinase substrates leading to melanin formation. The results support the evidence that TIQs were toxic toward melanoma cells, leading to their death by necrosis. TIQs toxicity was likely due to increased oxidative stress by generation of reactive oxygen species and oxidative metabolites. Our study represents an intent to furnish an additional contribution for the comprehension of catechol cytotoxicity.
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PMID:Cytotoxicity of dopamine-derived tetrahydroisoquinolines on melanoma cells. 1241 63

Our aim was 2-fold: to investigate the role of alpha-tocopherol supplementation on the antitumor activity of DDP and to evaluate the effect of alpha-tocopherol on the survival and neurotoxicity of DDP-treated mice. Experiments performed on the M14 human melanoma line demonstrated that alpha-tocopherol supplementation did not influence the efficacy of DDP; the inhibition of cell survival and of the in vivo tumor growth after treatment with alpha-tocopherol and DDP combination was similar to that observed after DDP alone. Conversely, alpha-tocopherol was also able to increase survival of mice treated with a high dose of DDP. While DDP alone produced death in about 70% of mice, the combination reduced deaths to about 30%. Analysis of oxidative stress markers and peroxidative damage in organs indicated that the protective effect of alpha-tocopherol was mainly related to its antioxidant activity. A significant increase in the concentration of TBARS and decreased PUFAs and catalase activity were observed after DDP treatment, while with alpha-tocopherol the levels of these markers were comparable to those observed in untreated mice. Histologic analysis performed on peripheral nerve revealed that alpha-tocopherol also protected mice from severe neurologic damage induced by DDP treatment. In conclusion, our results demonstrate that alpha-tocopherol protects against the systemic toxicity and neurotoxicity induced by DDP without interfering with its antitumor activity and suggest that this combination is a promising strategy to improve the therapeutic index of DDP-based chemotherapy.
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PMID:Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy. 1256 82

The activity of superoxide dismutase (SOD) and glutathione peroxidase (GSHPx), as well as the concentration of thiobarbituric acid reactive substances (TBARS) in tissues of transplantable melanoma in the golden hamster were measured and compared. Ten inbred male hamsters were used for the experiment. They were divided into two groups and were given Bomirski melanoma cells subcutaneously. The first group was given melanotic (Ma) melanoma cells. The second group was given amelanotic (Ab) melanoma cells. Thirty days after the transplantation the hamsters were dissected and the tumor tissues were taken and homogenized. A statistically significantly higher activity of the measured antioxidant enzymes was found in homogenates of Ma tumor than in homogenates of the Ab tumor. Activity of SOD is 8% higher in melanotic melanoma, 24% higher in CAT, and 45% higher in GSHPx. Statistically significant differences between TBARS concentrations were not confirmed. The higher activity of antioxidant enzymes in the melanotic tumor is a result of increased generation of oxygen-derived free radicals. It is presumed that it is strictly connected with intensified production of quinone and semiquinone radicals in the process of melanogenesis.
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PMID:Activity of antioxidant enzymes and concentrations of thiobarbituric acid reactive substances (TBARS) in melanotic and amelanotic Bomirski melanoma tissues in the golden hamster (Mesocricetus auratus, Waterhouse). 1258 88

Mevalonate pyrophosphate decarboxylase (MPD) is considered to be a cytosolic protein. Recently, other groups reported that MPD is mostly located in the peroxisomes. In this study, we examined whether the expression of MPD in mice depends on the proliferation of peroxisomes, and whether MPD is predominantly located in the peroxisomes or the cytosol of mice. No increase in the protein level of MPD was observed in the crude extract of the livers of mice administered with peroxisome proliferative drugs. The result suggests that the expression of MPD is independent of the proliferation of peroxisomes, and may be maintained via a specific regulatory mechanism, different from the regulation of the expression of peroxisome proliferator-activated receptor alpha. When the subcellular distribution of MPD in mouse melanoma (B16F10) cells was examined by cell fractionation, MPD was detected in the cytosol of B16F10 cells, but not in the peroxisomes. In permeabilized B16F10 cells treated with digitonin, which lack cytosolic enzymes, 80% and 20% of MPD, 75% and 25% of lactate dehydrogenase, or 2% and 98% of catalase, existed in the medium and in the cell, respectively. From these results, it indicated that MPD was predominantly located in the cytosol and did not exist in the peroxisomes of B16F10 cells.
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PMID:Subcellular distribution of mouse mevalonate pyrophosphate decarboxylase. 1273 93

We have demonstrated that blue light has anticancer effects in cultured cancer cells and tumor-bearing animals. Based on our experimental findings, in addition to cytostatic activity that suppresses the proliferation of B16 melanoma cells, blue light may exert cytocidal activity through interaction with vitamin(s) contained in the culture medium. The present study was undertaken to identify the specific vitamins with which blue light interacts and to investigate the factors responsible for its cytocidal activity. B16 melanoma cells were incubated in media supplemented with various vitamins and exposed to blue light for 10 min. Cell necrosis was observed only in media containing riboflavin (0.4 mg/l). The effects of other components of visible light on riboflavin were also studied. Riboflavin-containing media were exposed to light of each of the three primary colors (red, green and blue) and the effects on the colony-forming capacity of B16 melanoma cells were evaluated. Cell necrosis was induced only in media exposed to blue light. The effects of riboflavin increased in a concentration-dependent manner in the range from 0.3 to 1.0 mg/l in blue-light-exposed media and were antagonized by the presence of catalase (200 U/ml). These findings suggest that cell necrosis is probably induced by active oxygen species such as hydrogen peroxide formed by the reaction of riboflavin with blue light.
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PMID:Augmentation of the inhibitory effect of blue light on the growth of B16 melanoma cells by riboflavin. 1273 96

Melatonin, a derivative of tryptophan that is present in all vertebrates, was first described in bovine pineal gland. It is known that melatonin is a highly conserved molecule, present also in unicellular organisms and plants. Several effects of melatonin have been described, including receptor- and non-receptor-mediated actions. Herein, we studied the effects of melatonin on in vitro and in vivo cell proliferation of Cloudman S-91 murine melanoma cells. We demonstrated that melatonin treatment significantly inhibits S-91 melanoma cell proliferation in vitro (EC50 = 10-7 m) as well as reduces tumor growth in vivo. We also demonstrated that melatonin directly increases the activity of the antioxidant enzymes catalase and glutathione peroxidase. These effects are most likely triggered through the direct intracellular action of melatonin, since the presence of receptors could not be demonstrated in this cell line. Expression of MT-1 melatonin receptor by stable transfection, mediated a dramatic antiproliferative melatonin effect (EC50 = 10-10 m) in S-91 cells. The expressed receptor is negatively coupled to the adenylyl cyclase/cyclic AMP signaling pathway via Gi protein. These results suggest that expression of the MT-1 melatonin receptor in melanoma cells is a potential alternative approach to specifically target cells in cancer therapeutic treatment.
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PMID:MT-1 melatonin receptor expression increases the antiproliferative effect of melatonin on S-91 murine melanoma cells. 1500 12

The activity of antioxidant enzymes and the concentration of the lipid peroxidation product malondialdehyde (MDA) as indicator of oxidative damage were determined in selected tissues of healthy mice and transplanted B16 melanoma-bearing mice with increasing age. A total of 60 male mice were divided into 6 groups. Groups 1, 2 and 3 consisted of tumor-free, healthy mice aged 1, 9 and 16 months, respectively (average life span: 2 years). Groups 4, 5 and 6 consisted of mice of the same age as the healthy mice, but given intraperitoneally 10(6) cells of B16 melanoma for 2 weeks. An increase in the concentration of MDA was found in all the studied tissues (brain, liver, lungs, erythrocytes) and blood plasma of 16-month old healthy mice compared with the younger ones. The activity of superoxide dismutase (SOD) and catalase (CAT) was elevated in the brain and the activity of CAT and glutathione peroxidase (GPx) in the liver of aged healthy mice. The transplantation of melanoma caused an increase of the concentration of MDA and of the activity of all studied enzymes in all tissues. This elevation was most pronounced in the youngest mice group 4 and was higher than in the oldest healthy group 3. Thus, these early changes of the "(anti-)oxidative status" in the investigated tissues caused by the tumor development have similarities with age-associated alterations of healthy mice, especially in regard to MDA in all tissues or SOD and CAT in brain.
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PMID:Activity of antioxidant enzymes and concentration of lipid peroxidation products in selected tissues of mice of different ages, both healthy and melanoma-bearing. 1522 38

The incidence rate of melanoma is higher in fair-skinned than in dark-skinned individuals. In negroid skin there is more eumelanin which is present in all skin layers and fewer polyunsaturated fatty acids (PUFA) than in caucasoid skin. The western diet, which is rich in omega-6 polyunsaturated fatty acids, is associated with more proneness to cancer including cutaneous melanoma. To study the respective influence of omega-6 PUFA and low phototype melanocytes on redox status -basal and following UV irradiation-, we used epidermal reconstructs. The addition of polyunsaturated fatty acids as well as the presence of low phototype melanocytes affected basal status similarly except for catalase activity, which decreased significantly in polyunsaturated fatty acid-supplemented reconstructs. Following UV, polyunsaturated fatty acids and low phototype melanocytes increased lipid and protein oxidative damage without affecting direct DNA damage. However, polyunsaturated fatty acids increased epidermal apoptosis whereas low phototype melanocytes decreased it. Since our data suggest that an omega-6 PUFA rich-diet may increase oxidative damage in melanocytes without inducing apoptosis, the long-term net outcome could be cumulated mutations and an increased risk of skin cancer, especially melanoma.
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PMID:Polyunsaturated fatty acids partially reproduce the role of melanocytes in the epidermal melanin unit. 1574 May 92

Mutations in two loci encoding cell-cycle-regulatory proteins have been shown to cause familial malignant melanoma. About 20% of melanoma-prone families bear a mutation in the CDKN2A locus, which encodes two unrelated proteins, p16INK4A and p14ARF. Mutations in the other locus, CDK4, are much rarer and have been linked to the disease in only three families worldwide. In the 1960s, a large Norwegian pedigree with multiple atypical nevi and malignant melanomas was identified. Subsequently, six generations and more than 100 family members were traced and 20 cases of melanoma verified. In this article, we report that CDK4 codon 24 is mutated from CGT to CAT (Arg24His) in this unusually large melanoma kindred. Intriguingly, one of the family members had ocular melanoma, but the CDK4 mutation could not be detected in archival tissue samples from this subject. Thus, the case of ocular melanoma in this family was sporadic, suggesting an etiology different from that of the skin tumors. The CDK4 mutation in the Norwegian family was identical to that in melanoma families in France, Australia, and England. Haplotype analysis using microsatellite markers flanking the CDK4 gene and single-nucleotide polymorphisms within the gene did not support the possibility that there was a common founder, but rather indicated at least two independent mutational events. All CDK4 melanoma families known to date have a substitution of amino acid 24. In addition to resulting from selection pressure, this observation may be explained by the CG dinucleotide of codon 24 representing a mutational hot spot in the CDK4 gene.
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PMID:A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation. 1588 May 89


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