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 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

B-16 melanoma cells in culture were prelabeled with (3H)-arachidonate, and exposed to UV radiation. Immediately after irradiation the cells released labeled materials. This UV-stimulated release was inhibited by mepacrine (20 microM) and calmodulin inhibitor W7 (0.5 microM). To determine the influence of extracellular Ca2+ on the UV-stimulated release, experiments were made with media containing various concentrations of Ca2+. The release decreased significantly at lower Ca2+ concentrations. These results suggest that Ca2+-calmodulin-dependent phospholipase A2 was involved in UV-stimulated release of radiolabeled materials, possibly arachidonic acid and its metabolites, from the cells.
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PMID:Effect of UV-B irradiation on release of arachidonic acid from B-16 melanoma cells. 271 Jul 98

Thioredoxin reductase has been purified from human metastatic melanotic melanoma and amelanotic melanoma tissues. Enzyme from the melanotic melanoma tissue contains bound calcium showing classical sigmoidal allosteric kinetics, whereas enzyme from the amelanotic melanoma yielded normal Michaelis-Menten saturation with substrate. Calcium inhibition can be partially reversed by oxidized thioredoxin. 45Ca has been used to label the amelanotic melanoma enzyme in order to determine the number of calcium-binding sites. These isotope experiments yielded only one calcium-binding site per enzyme molecule. Enzyme labeled with 45Ca was dialyzed for 24 h without loss of radioactivity, but the addition of oxidized thioredoxin to this labeled enzyme caused 60% calcium exchange in 24 h. Comparative studies with Escherichia coli thioredoxin reductase showed similar calcium inhibition as well as partial reactivation with oxidized thioredoxin. The enzyme from E. coli previously sequenced by others, showed considerable homology with the first EF-hands calcium-binding site of calmodulin. Detailed calcium-binding studies indicated that 10(-5) M of this fast exchange ion was sufficient to cause allosteric regulation in 10 min. This strong calcium-binding property could explain the allosteric nature of the thioredoxin reductase purified from human metastatic melanotic melanoma and its role in the regulation of melanin biosynthesis.
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PMID:Calcium regulates thioredoxin reductase in human metastatic melanoma. 276 62

Electron spin resonance spectroscopy has been used to measure the reduction of nitroxide radicals on a spin-labeled quaternary ammonium substrate by plasma membrane-associated thioredoxin reductase (EC 1.6.4.5) at the surface of cutaneous and subcutaneous melanoma metastases from one patient (B.M.). Enzyme activity in these metastases was shown to be hyperactive compared to normal skin and was subject to inhibition by calcium. From the remainder of the tissue (50.6 g), plasma membrane-associated thioredoxin reductase has been isolated and its molecular properties were compared with the same enzyme purified from the cytosol of rat liver and Escherichia coli. The enzyme from melanoma possessed an identical molecular weight to that from rat liver as determined by SDS-polyacrylamide gel electrophoresis (Mr 58,000). Upon fluorescence spectroscopic examination, the enzyme from melanoma was shown to contain flavin adenine dinucleotide as previously shown in the enzymes from E. coli and rat liver. The increased activities in plasma membrane-associated thioredoxin reductase in metastases of malignant melanotic melanoma are discussed in terms of the cellular functions of this important enzyme.
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PMID:The activity and purification of membrane-associated thioredoxin reductase from human metastatic melanotic melanoma. 284 80

Calcium ionophore A23187 lowers basal levels of tyrosinase and inhibits the MSH-induced increase in tyrosinase in Cloudman S-91 mouse melanoma cell cultures. Ionophore at a concentration of 10(-6) g/ml causes a 50% reduction in basal levels of tyrosinase and inhibits the MSH stimulated level of enzyme. Ionophore A23187 also inhibits the PGE1 mediated stimulation of tyrosinase, as well as the rise in enzyme activity observed in cells exposed to either theophylline (1 mM) or dbcAMP (10(-4)M). Ionophore does not affect basal levels of cyclic AMP nor the elevated levels produced by either MSH or PGE1, suggesting then, that the antagonistic activity of A23187 is localized to a point in the pathway of tyrosinase activation distal to the formation of cAMP. Ionophore causes a rapid and marked (greater than 50%) inhibition of cellular protein synthesis and it is possible that this calcium mobilizing compound may exert its inhibitory effects on tyrosinase activity by causing a general reduction in cellular translation. Since the inhibition of protein synthesis occurs in cells exposed to ionophore in either the presence or absence of calcium in the medium, it seems, likely that the ionophore may exert its effects by causing the release of calcium from intracellular sites.
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PMID:Inhibition of tyrosinase activity and protein synthesis in melanoma cells by calcium ionophore A23187. 285 56

The majority of melanocytic tumours are easily diagnosed but they become a problem when they are amelanotic and the tumour cells resemble those of other tumours. This applies particularly to secondary melanoma. Detection of S100 protein is a useful identifying marker. S100 protein, so named for its solubility in saturated ammonium sulphate, is derived from brain tissue. It is a dimer and belongs to a calcium binding group of proteins. The protein was first thought to be in neural or neural crest derived tissues but has been found in chondrocytes, adipocytes, myoepithelial cells, dendritic cells of lymphoid tissue, Langerhans cells and T lymphocytes. The protein is present in a high proportion of malignant melanomas and nevocytic nevi of skin, but is less positive in eye melanomas. It is present in gliomas, Schwannomas and neurofibromas but not in neurone derived tumours such as neuroblastomas. Chondromas, chondrosarcomas, liposarcomas, some osteogenic sarcomas and some histiocytic tumours are positive. The tumours that do not contain S100 protein are listed. Pending development of melanoma-directed monoclonal antibodies, the use of anti-serum to S100 protein plus anti-keratin and anti-leukocyte reagents is useful in the identification of tumours of doubtful histogenesis.
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PMID:S-100 protein as a marker for melanocytic and other tumours. 299 6

We tested the influence of daily subcutaneous injections of 12.5 and 25 pmol of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the growth of tumors arising from intracutaneous inoculations of athymic nude mice with rat osteogenic sarcoma cells (ROS) and human melanoma cells. Both doses of 1,25(OH)2D3 increased plasma calcium levels after 3 weeks and produced a striking enhancement in tumor weight when the mice received 1,25(OH)2D3 receptor-rich ROS17/2.8 cells. In contrast, 1,25(OH)2D3 caused no consistent effect on tumor weight in mice given G-361 melanoma cells with low receptor copy number or receptor deficient ROS 24/1 cells. Thus, 1,25(OH)2D3 stimulated tumor growth in a receptor dependent fashion, in vivo, instead of inhibiting it as predicted from the reduction of proliferation of cultured cells in the presence of 1,25(OH)2D3.
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PMID:1,25-Dihydroxyvitamin D3 enhances the growth of tumors in athymic mice inoculated with receptor rich osteosarcoma cells. 302 Nov 53

It has been demonstrated previously that several human cancer cell lines possess specific, high affinity receptors for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3, calcitriol] and that 1,25-(OH)2D3 and certain of its metabolites inhibit the growth in vitro of several human breast cancer and malignant melanoma cell lines, i.e., analogous to the effect of estrogens on breast cancer. Furthermore, it has been shown that 1,25-(OH)2D3 and one of its synthetic analogues prolonged the survival in mouse leukemia, induced by inoculation of leukemic cells into syngeneic mice. However, until now no growth-inhibitory effect of 1,25-(OH)2D3 has been demonstrated in vivo for human cancer cells or for solid cancers. This paper describes the suppression by 1,25-(OH)2D3 of the growth of human cancer cell-derived xenografts in immune-suppressed mice. However, the 24-hydroxylated metabolite and the 24-difluorinated analogue of 1,25-(OH)2D3, both of which are active in vitro, were ineffective in this xenograft model system. The suppression by 1,25-(OH)2D3, which was achieved without significant toxicity, was observed with xenografts derived from two 1,25-(OH)2D3 receptor-positive cell lines (COLO 206F, derived from a colonic cancer, and COLO 239F from a malignant melanoma) but not in those from a receptor-negative line (RPMI 7932, also derived from a malignant melanoma). These studies demonstrate that pharmacological doses of 1,25-(OH)2D3 can be tolerated in the presence of a low calcium diet and that these doses can suppress the growth of human solid xenograft tumors in vivo. This is the first report of 1,25-(OH)2D3 growth suppression of solid tumors derived from human cancer cells in an in vivo model system, and it supports the hypothesized potential of the hormone in the treatment of 1,25-(OH)2D3 receptor-positive human cancers.
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PMID:Suppression of in vivo growth of human cancer solid tumor xenografts by 1,25-dihydroxyvitamin D3. 302 16

Binding of beta-melanotropin (beta-MSH) and subsequent activation of adenylate cyclase in the M2R mouse melanoma cell line is strongly dependent on the concentration of extracellular free calcium. This effect can be demonstrated both in the intact cell and in a plasma membrane preparation derived therefrom, using an EGTA buffer system. In contrast, stimulation of adenylate cyclase by prostaglandin E1, forskolin, or guanosine 5'-O-(2-thiotriphosphate) is calcium insensitive. It is shown that calcium increases the binding affinity of beta-MSH for its receptor by a factor of 20 (from 400 nM to 20 nM) without affecting maximal hormone binding. At supersaturating concentrations of beta-MSH (greater than 200 nM) binding gradually becomes calcium independent. Hormone-receptor complexes formed in the presence of calcium dissociated rapidly (less than or equal to 2 min) and reversibly upon the elimination of calcium by excess EGTA. Among nine divalent metal cations tested, calcium was found to be the most effective in facilitating hormone binding. Whereas calcium promotes beta-MSH binding, GTP and its stable analogs lead to a reduction in both maximal binding (65%) and affinity (2-fold). These effects are calcium independent, suggesting that the reciprocal control of beta-MSH binding by calcium and guanosine nucleotides is mediated by two separate and independent mechanisms.
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PMID:Dual regulation of beta-melanotropin receptor function and adenylate cyclase by calcium and guanosine nucleotides in the M2R melanoma cell line. 302 27

The classic function of 1,25-dihydroxyvitamin D3, the hormonally active form of vitamin D, is the maintenance of normal levels of calcium and phosphorus in the blood. 1,25-Dihydroxyvitamin D3 binds to a specific receptor protein and exerts its biologic action by a mechanism analogous to that proposed for other steroid hormones, that is, the receptor-ligand complex acts on the chromatin to induce transcription of specific genes. Intracellular receptors that bind 1,25-dihydroxyvitamin D3 with high affinity have been found in a large number of tumor cell lines examined as melanoma, osteosarcoma, and human breast and colonic carcinoma cells. The 1,25-dihydroxyvitamin D3 receptor in these cells has characteristics similar to the receptor in bone and intestine, the known target tissues of the hormone. In fact, 1,25-dihydroxyvitamin D3 inhibits the proliferation of melanoma, osteosarcoma, and breast carcinoma cells. More recently, 1,25-dihydroxyvitamin D3 has been shown to suppress the growth and induce monocytic differentiation of murine and human myeloid leukemia cells in vitro. These results point to a previously unsuspected involvement of vitamin D in cell proliferation and differentiation and suggest that analogs of the vitamin D hormone may be of interest as possible therapeutic agents in the treatment of malignancy.
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PMID:The relationship between the vitamin D system and cancer. 303


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