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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of insulin on melanogenesis were examined in human Swift melanoma cells. When these cells were grown in a chemically defined culture medium containing insulin (5 microg/ml), they showed a low pigmentation in association with a high activity of glutathione peroxidase (GPO) and a low activity of tyrosinase. In Eagle's minimum essential medium supplemented with foetal calf serum (EMEM-FCS), the Swift cells showed an intense pigmentation in association with a low GPO activity and a high tyrosinase activity. Modulation of GPO activity with sodium selenite had no effect on melanogenesis variables. In contrast, addition of insulin (5 microg/ml) to the EMEM medium led to a marked decrease in tyrosinase activity (p<0.001) and to a concomitant reduction in the levels of 5-S-cysteinyldopa (p <0.01). These results indicate that insulin inhibits the formation of 5-S-cysteinyldopa and that of melanin via the inhibition of tyrosinase activity.
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PMID:Insulin inhibits tyrosinase activity and 5-S-cysteinyldopa formation in human melanoma cells. 922 19

Various investigations have reported the occurrence in bacterial and mammalian cells of an adaptive response to the toxic effects of oxidants or agents that cause oxidation via redox reactions. In our previous study, it was shown that several cell lines pretreated with a low dose of hydrogen peroxide (H2O2) exhibited an adaptive response to subsequent high doses of adriamycin (ADR), whereas other cell lines did not. Based on the observation that the cell lines utilized differed in their sensitivity towards adriamycin, we undertook the present investigation with the goal of evaluating possible relationships between the levels of antioxidant enzymes and sensitivity towards adriamycin. Another aim was to determine relationships between the inducibility of these enzymes and the occurrence of adaptation. We utilized African Green monkey kidney (V3), human embryo (CLV98), human melanoma (ME18), and Chinese hamster ovary (CHO) cell lines and experimentally developed adriamycin-resistant human melanoma (ME18/RN) and Chinese hamster ovary (CHO/RN) cell sublines. Cytotoxicity was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and trypan blue exclusion. The levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were determined in the same kind of experiment as that revealing the occurrence of adaptation. The rank order established for catalase activities was similar to that for sensitivity towards adriamycin. Aberrant increases in the tested enzymes were demonstrated in experimental groups of all kinds of cells. We conclude that in our cell systems catalase is a major determinant of adriamycin resistance. Whether the occurrence of the adaptive response under study is dependent on the contribution of catalase, itself dependent on the degree of resistance to the drug, is discussed.
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PMID:Studies on adaptation to adriamycin in cells pretreated with hydrogen peroxide. 933 76

Five human melanoma cell lines were investigated for their antioxidant activities. These metabolic data were correlated with cytogenetic analysis giving the relative numbers of chromosomes or chromosomal segments carrying the gene encoding for each enzyme. Particular attention was focused on the expression of superoxide dismutase 2 (SOD2), whose gene, located on the long arm of chromosome 6 (6q), has been proposed as a tumour suppressor gene. The activity of glutathione peroxidase (GPX), glutathione reductase (GSR) and catalase appeared to be unrelated to the relative number of 3q, 8p and 11p arms which, respectively, carry their encoding genes. GPX activity paralleled that of total SOD activity, and GSR variations followed those of GPX, suggesting possible metabolic regulation. Both the activity and the amount of SOD1 immunoreactive protein correlated with the number of chromosomes 21, suggesting a gene dosage effect. The three cell lines with deletions of the 6q arm had lower SOD2 activity and less immunoreactive protein than the two cell lines without 6q deletion. In addition, they demonstrated high thymidine kinase and thymidylate synthetase activities, which are directly linked to the cell proliferation rate. These results strengthen the hypothesis that SOD2 has a function as a tumour suppressor gene, but also suggest that the expression of other antioxidant enzymes might be altered in human melanomas.
Melanoma Res 1998 Aug
PMID:Modifications of the antioxidant enzymes in relation to chromosome imbalances in human melanoma cell lines. 976 8

The activities of antioxidant enzymes, and the expression of p21(WAF1) and p53 proteins were studied at different times after subculture during proliferation and differentiation phases. Two human melanoma cell lines were used: IPC182, which is a non-differentiating cell line, and IGR221, which spontaneously differentiates at the end of the exponential growth phase, as evidenced by a marked increase of melanin content and tyrosinase activity. In the two cell lines, the slowing of proliferation coincided with an increase in the activity and amount of immunoreactive superoxide dismutases (SOD1 and SOD2), and a decrease of catalase and glutathione peroxidase activities, and of the glutathione content. The levels of p21WAF1 and p53 proteins were found to be lower in confluent than in proliferative cells. Several parameters were modified only during the differentiation phase of IGR221 cells; in these cells the increase of tyrosinase activity was highly correlated with the increase in SOD2, GST, glutathione reductase, and G6PD activities. The level of glutathione was found to be lower in differentiated IGR221 than in non-differentiated IPC182 cells. These results suggest that p21WAF1 and p53 proteins are not involved in the spontaneous differentiation process of melanoma cells, and that abnormal regulation of the cell cycle inhibition pathway occurred in these cells. The results sustain the hypothesis that alterations of antioxidant enzyme expression are involved in the control of proliferation and differentiation of melanoma cells. Alterations of SOD2 activity may be of particular importance, since variations are observed with both cell growth and cell differentiation.
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PMID:Modulation of antioxidant enzymes p21WAF1 and p53 expression during proliferation and differentiation of human melanoma cell lines. 1023 48

We have studied whole blood glutathione peroxidase activity as a possible diagnostic factor or marker for detection and diagnosis of patients with melanoma. This activity was determined in 40 melanoma patients (MP) and in 40 healthy persons (HP) using an enzymatic method. We found a mean value of 17.90+/-6.82 units/ml in MP and 27.07+/-14.35 units/ml in HP. A very significant decrease in whole blood glutathione peroxidase activity was observed in MP in comparison to the enzymatic activity in HP (P = 0.0005). In order to check whether this test could discriminate between MP and HP, a complete statistical Receiver Operating Characteristic (ROC) curve analysis was performed. The cut-off value was 14.26 units/ml. The area under the curve was 0.737. According to these results, the test could discriminate adequately between both groups. However, the high specificity and low sensitivity values associated with that cut-off value would make this test a very valuable tool for confirming the detection, rather than for primary screening.
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PMID:Whole blood glutathione peroxidase activity in melanoma patients. 1050 74

The flavonoid antioxidant silymarin is used clinically in Europe and Asia for the treatment of liver diseases and is sold in the United States and Europe as a dietary supplement. Recently we showed that silymarin possesses exceptionally high cancer-preventive effects in different mouse skin carcinogenesis models and affords strong anticancer effects in human skin, cervical, prostate, and breast carcinoma cells. More recently, we showed that the anti-tumor-promoting effect of silymarin is primarily targeted against stage I tumor promotion in mouse skin (Cancer Res 1999;59:622-632). Based on this recent study, in this report, further investigations were made to identify and define the biochemical and molecular mechanisms of silymarin's effect during stage I tumor promotion in mouse skin. A single topical application of silymarin at 3-, 6-, and 9-mg doses onto SENCAR mouse skin followed 30 min later with 12-O-tetradecanoylphorbol 13-acetate (TPA) at a 3-microg dose resulted in a 76-95% inhibition (P < 0.001) of TPA-caused skin edema. Similarly, these doses of silymarin also showed 39-90%, 29-85%, and 15-67% protection (P < 0.05 or 0.001), against TPA-caused depletion of epidermal superoxide dismutase, catalase, and glutathione peroxidase activity, respectively. Pretreatment of mice with silymarin also produced highly significant inhibition of TPA-caused induction of epidermal lipid peroxidation (47-66% inhibition, P < 0.001) and myeloperoxidase activity (56-100% inhibition, P < 0.001). In additional studies assessing the effect of silymarin on arachidonic acid metabolism pathways involving lipoxygenase and cyclooxygenase (COX), similar doses of silymarin showed highly significant inhibition of TPA-caused induction of epidermal lipoxygenase (49-77% inhibition, P < 0.001) and COX (35-64% inhibition, P < 0.01 or 0.001) activity. Western immunoblot analysis showed that the observed effect of silymarin on COX activity was due to inhibition of TPA-inducible COX-2 with no change in constitutive COX-1 protein levels. In other studies, silymarin also showed dose-dependent inhibition of TPA-caused induction of epidermal interleukin 1alpha (IL-1alpha) protein (39-72% inhibition, P < 0.005 or 0.001) and mRNA expression. Taken together, the results from these biochemical and molecular studies further substantiate our recent observation of silymarin's anti-tumor-promoting effects primarily at stage I tumor promotion. Furthermore, the observed inhibitory effects of silymarin on COX-2 and IL-1alpha should be further explored to develop preventive strategies against those cancers in which these molecular targets play one of the causative roles, such as non-melanoma skin, colon, and breast cancers in humans.
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PMID:Significant inhibition by the flavonoid antioxidant silymarin against 12-O-tetradecanoylphorbol 13-acetate-caused modulation of antioxidant and inflammatory enzymes, and cyclooxygenase 2 and interleukin-1alpha expression in SENCAR mouse epidermis: implications in the prevention of stage I tumor promotion. 1056 9

We have previously shown that alpha-melanocyte-stimulating hormone (alpha-MSH) can oppose tumor necrosis factor alpha activation of NF-kappaB (1-2 h) and intercellular adhesion molecule 1 up-regulation (mRNA by 3 h and protein by 24 h) in melanocytes and melanoma cells. The present study reports on the ability of four MSH peptides to control intracellular peroxide levels and glutathione peroxidase (GPx) activity in pigmentary and nonpigmentary cells. In human HBL melanoma and HaCaT keratinocytes tumor necrosis factor alpha and H(2)O(2) both activated GPx in a time- and concentration-dependent manner (by 30-45 min). alpha-MSH peptides were found to inhibit the stimulated GPx activity and had biphasic dose-response curves. MSH 1-13 and MSH [Nle(4)-d-Phe(7)] achieved maximum inhibition at 10(-10) and 10(-12) m, respectively. Higher concentrations (10-100 fold) of MSH 4-10 and MSH 11-13 were required to produce equivalent levels of inhibition. alpha-MSH was also capable of reducing peroxide accumulation within 15 min, and again this inhibition was biphasic. The data support a role of alpha-MSH in acute protection of cells to oxidative/cytokine action that precedes NF-kappaB and GPx activation. The rapidity and potency of the response to alpha-MSH in pigmentary and nonpigmentary cells suggest this to be a central role of this peptide in cutaneous cells.
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PMID:Alpha-melanocyte-stimulating hormone reduces impact of proinflammatory cytokine and peroxide-generated oxidative stress on keratinocyte and melanoma cell lines. 1082 44

The transcription factor nuclear factor-kappaB (NF-kappaB) is constitutively activated in malignancies from enhanced activity of inhibitor of NF-kappaB (IkappaB) kinase, with accelerated IkappaBalpha degradation. We studied whether redox signaling might stimulate these events. Cultured melanoma cells generated superoxide anions (O(2)(-)) without serum stimulation. O(2)(-) generation was reduced by the NAD(P)H:quinone oxidoreductase (NQO) inhibitor dicumarol and the quinone analog capsaicin, suggesting that electron transfer from NQO through a quinone-mediated pathway may be an important source of endogenous reactive oxygen species (ROS) in tumor cells. Treatment of malignant melanoma cells with the H(2)O(2) scavenger catalase, the sulfhydryl donor N-acetylcysteine, the glutathione peroxidase mimetic ebselen, or dicumarol decreased NF-kappaB activation. Catalase, N-acetylcysteine, ebselen, dicumarol, and capsaicin also inhibited growth of melanoma and other malignant cell lines. These results raise the possibility that ROS produced endogenously by mechanisms involving NQO can constitutively activate NF-kappaB in an autocrine fashion and suggest the potential for new antioxidant strategies for interruption of oxidant signaling of melanoma cell growth.
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PMID:Reactive oxygen species from NAD(P)H:quinone oxidoreductase constitutively activate NF-kappaB in malignant melanoma cells. 1117 86

The mechanism of NO- and H(2)O(2)-induced tumor cytotoxicity was examined during B16 melanoma (B16M) adhesion to the hepatic sinusoidal endothelium (HSE) in vitro. We used endothelial nitric-oxide synthetase gene disruption and N(G)-nitro-l-arginine methyl ester-induced inhibition of nitric-oxide synthetase activity to study the effect of HSE-derived NO on B16M cell viability. Extracellular H(2)O(2) was removed by exogenous catalase. H(2)O(2) was not cytotoxic in the absence of NO. However, NO-induced tumor cytotoxicity was increased by H(2)O(2) due to the formation of potent oxidants, likely ( small middle dot)OH and (-)OONO radicals, via a trace metal-dependent process. B16M cells cultured to low density (LD cells), with high GSH content, were more resistant to NO and H(2)O(2) than B16M cells cultured to high density (HD cells; with approximately 25% of the GSH content found in LD cells). Resistance of LD cells decreased using buthionine sulfoximine, a specific GSH synthesis inhibitor, whereas resistance increased in HD cells using GSH ester, which delivers free intracellular GSH. Because NO and H(2)O(2) were particularly cytotoxic in HD cells, we investigated the enzyme activities that degrade H(2)O(2). NO and H(2)O(2) caused an approximately 75% (LD cells) and a 60% (HD cells) decrease in catalase activity without affecting the GSH peroxidase/GSH reductase system. Therefore, B16M resistance to the HSE-induced cytotoxicity appears highly dependent on GSH and GSH peroxidase, which are both required to eliminate H(2)O(2). In agreement with this fact, ebselen, a GSH peroxidase mimic, abrogated the increase in NO toxicity induced by H(2)O(2).
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PMID:Tumoricidal activity of endothelial cells. Inhibition of endothelial nitric oxide production abrogates tumor cytotoxicity induced by hepatic sinusoidal endothelium in response to B16 melanoma adhesion in vitro. 1131 48

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


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