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 melanocytotoxic effects of 4-hydroxyanisole (4-OHA) are thought to depend upon its conversion to toxic oxidation products by the enzyme tyrosinase. In this study, the cytotoxicity of 4-OHA was examined in different B16 melanoma cell lines that show varying levels of tyrosinase and after stimulation by melanocyte-stimulating hormone (MSH) and all-trans-retinoic acid (RA). 4-OHA decreased cell survival of three melanotic and one amelanotic cell line in culture, but the effect was unrelated to their tyrosinase activity or the subcellular localization of the enzyme. Although stimulation of tyrosinase activity with RA enhanced the cytotoxicity of 4-OHA, no similar enhancement occurred with alpha-MSH. It appears that there is no relationship between the cytotoxic effects of 4-OHA and intracellular tyrosinase and the enhancement of its cytotoxicity by RA may well be related to the antiproliferative effects of the retinoid.
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PMID:Cytotoxicity of 4-hydroxyanisole and tyrosinase activity in variant cell lines of B16 melanoma. 285 44

The basal secretion of proteo-hormones alpha-MSH and ACTH in plasma as well as the changes of the plasma concentrations following UV A-whole-body irradiation were investigated on 40 young male volunteers with different pigmentation levels (Caucasians: skin types I, II, III. Blacks: skin type VI). Significantly lower mean basic values of alpha-MSH and ACTH of light-haired persons in comparison with dark-haired and black persons (p less than 0,05) were demonstrated. We observed furthermore a significant increase of these proteo-hormones (alpha-MSH: skin type I: 26,7%, skin type II: 22,7%) in persons less pigmented within a short time after UV A whole-body irradiation in contrast to the more pigmented volunteers. These results prove a cutaneous peripheral sensor for UV A-rays, reacting with a different sensitivity depending on disposition and inducing endocrinological reactions. How this cutaneous-hypothalamic-pituitary stimulus mediation functions in detail is not completely revealed up to now. In what respect the present results, which can be explained as a consequence of evolutionary development, have a connection with the induction of melanoma remains to be seen.
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PMID:[Endocrinological reactions following UV A whole body irradiation]. 298 4

The fluorescein-labeled melanotropin [N alpha-chlorotriazinylaminofluorescein-Ser1,Nle4,D-Phe 7]-alpha-MSH, was prepared by solid-phase techniques of peptide synthesis. The biological actions of this analogue were determined in several melanocyte bioassays and were compared with the parent peptide [Nle4,D-Phe7]-alpha-MSH and the native hormone alpha-MSH. The fluorescein compound was a superpotent agonist with approximately 10 times more activity than alpha-MSH in both the frog and the lizard skin bioassays. Murine S91 melanoma cells assayed in vitro (tyrosinase bioassay) were as responsive to the fluorescein analogue as to alpha-MSH. The analogue exhibited ultraprolonged biological activity and the biological activities were unaffected by treatment of the analogue with alpha-chymotrypsin. The fluorescein-labeled melanotropin should prove useful for melanotropin receptor characterization.
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PMID:Synthesis and biological evaluation of the superagonist [N alpha-chlorotriazinylaminofluorescein-Ser1,Nle4,D-Phe7]-al pha-MSH. 298 82

alpha-Melanotropin (alpha-melanocyte stimulating hormone, alpha-MSH) stimulates tyrosinase activity in Cloudman S91 murine melanoma cells. Three [Nle4, D-Phe7]-substituted alpha-melanotropin analogues, [Nle4, D-Phe7]-alpha-MSH, Ac-[Nle4, D-Phe7]-alpha-MSH4-11-NH2, and Ac-[Nle4, D-Phe7]-alpha-MSH4-10-NH2, are at least 100-fold more effective than alpha-MSH in stimulating melanoma tyrosinase, the rate-limiting enzyme in melanin biosynthesis. These [Nle4, D-Phe7]-substituted melanotropin analogues induce tyrosinase activity in melanoma cells with shorter contact times than required by the native hormone, alpha-MSH. [Nle4, D-Phe7]-substituted melanotropins also induce a prolonged (residual) stimulation of melanoma tyrosinase. Following incubation of melanoma cells in the presence of [Nle4, D-Phe7]-alpha-MSH for 24 h, tyrosinase activity is maintained for up to 6 days in the absence of the melanotropin. The shorter 4-10 and 4-11 fragment analogues also exhibit residual melanotropic activity. The prolonged stimulation of tyrosinase in the absence of the analogues is maintained even though melanoma cells continue to divide about every 24 h. These results suggest that melanoma cells possess spare melanotropin receptors and that [Nle4, D-Phe7]-substituted analogues bind almost irreversibly to these receptors or to some other component of the adenylate cyclase enzyme complex responsible for enhancing tyrosinase activity and melanin production.
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PMID:Prolonged stimulation of S91 melanoma tyrosinase by [Nle4, D-Phe7]-substituted alpha-melanotropins. 299 67

The biological activity and a possible modulatory role of the N-terminal tetrapeptide Ser-Tyr-Ser-Met from alpha-MSH/ACTH was tested in the Anolis melanophore assay, the Xenopus melanophore assay, tyrosinase stimulation in mouse melanoma cells and in excessive grooming in the rat. ACTH1-4 did not exhibit biological activity in any of these four assays nor did it have modulatory properties in the Xenopus and the melanoma cell assay. However, in the Anolis assay ACTH1-4 potentiated pigment dispersion induced by alpha-MSH, alpha-MSH5-13 and ACTH1-24 by a factor of about 2. In the grooming assay ACTH1-4 potentiated the effects of alpha-MSH, alpha-MSH5-13, ACTH1-16 and ACTH5-16, but not those of ACTH1-24. Oxidized ACTH1-4 was without biological activity and potentiating properties in all four assays. This study shows that small fragments of the pro-opiomelanocortin precursor, which are devoid of biological activity, can modulate peripheral and central actions of alpha-MSH/ACTH.
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PMID:ACTH1-4 potentiates alpha-MSH-induced melanophore dispersion and excessive grooming. 301 87

We have examined adenylate cyclase (AC) in the M2R melanoma cell line, a novel clone of transplantable B16 melanoma cells. It has been found that activity of this enzyme is highly responsive to beta-melanotropin (beta-MSH) and other hormones possessing melanotropic activity (e.g., alpha-melanotropin (alpha-MSH) and adrenocorticotrophic hormone (ACTH1-24)). beta-MSH stimulation of adenylate cyclase, both in the intact cell and in a plasma membrane-enriched fraction derived thereof, was shown to be saturable and dose-dependent. In addition, prostaglandin E1 (PGE1) was found to be a potent stimulator of AC activity in these cells. Hormone stimulation of enzyme activity in the intact cell was strongly potentiated by forskolin which not only enhanced maximal AC activity 3-fold, but lowered by 40-fold the concentration of beta-MSH required for half-maximal stimulation. Using biologically active [125I]iodo-beta-MSH prepared in our laboratory we have examined the specificity of beta-MSH binding to its receptor in both intact M2R cells and plasma membranes derived thereof. Among a series of hormones tested only alpha-MSH and ACTH1-24 competed with [125I]iodo-beta-MSH for binding to the melanotropin receptor in accordance with the results obtained with AC. In contrast to the strong effect on cyclic 3',5'-adenosine monophosphate (cAMP) accumulation in M2R cells forskolin has no effect on [125I]iodo-beta-MSH binding. It appears that the kinetic properties of beta-MSH binding and beta-MSH stimulation of adenylate cyclase activity are essentially identical, the half-maximal effects of which are demonstrated at approximately 20 nM beta-MSH.
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PMID:Regulation of adenylate cyclase by beta-melanotropin in the M2R melanoma cell line. 301 5

alpha-MSH (melanocyte-stimulating hormone) causes an increase in tyrosinase activity (O-diphenol-O2 oxidoreductase; EC 1.14.18.1) in Cloudman S-91 mouse melanoma cell cultures following a lag period of approximately 9 h. Treatment of cells with 2 X 10(-7)M alpha-MSH for 6 days results in a 90-fold increase in the specific activity of the enzyme. The hormone-mediated increase in tyrosinase activity is dependent upon continued transcription since the enzyme induction is suppressed by either cordycepin (1 microgram/ml) or alpha-amanitin (10 micrograms/ml). Immunoprecipitation analysis of pulse-labeled tyrosinase from control and MSH-treated cultures (48-h exposure) has demonstrated that MSH stimulates tyrosinase synthesis by approximately 4-fold, a level of induction which does not correspond to the observed 14-fold increase in enzyme activity. When immunotitration curves were developed from cell extracts of control and MSH-treated cultures using immunoprecipitation and competitive enzyme-linked immunosorbent assay protocols, evidence for the presence of immunologically active but catalytically less active enzyme in untreated melanoma cell cultures was demonstrated. Degradation rates of tyrosinase were found to be similar in control cultures or in cells treated with MSH for up to 48 h. Taken together, these results suggest that in addition to stimulating tyrosinase synthesis, MSH may also promote an increase in the catalytic efficiency of the enzyme.
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PMID:Alpha-melanocyte-stimulating hormone regulation of tyrosinase in Cloudman S-91 mouse melanoma cell cultures. 303 Oct 58

Cell density is a factor that affects the capacity of Cloudman S91 melanoma cells to respond to melanotropins in monolayer culture. Continuous exposure of melanoma cells to alpha-melanotropin or its potent analog [Nle4, D-Phe7]-alpha-MSH, resulted in maximal stimulation of tyrosinase after 2 d of treatment, but the magnitude of stimulation decreased thereafter despite the continued presence of the melanotropins. However, when melanoma cells continually exposed to melanotropins were subcultured to an initial low cell density and maintained in contact with alpha-MSH or [Nle4, D-Phe7]-alpha-MSH (long-term culture), tyrosinase activity was rapidly restored and greatly enhanced. Also, when cells were seeded at initial densities ranging from 0.2 to 3.2 X 10(6) cells/flask, and exposed for 24 h to 10(-7) M alpha-MSH, only the cultures seeded at low densities (0.2 and 0.4 X 10(6) cells/flask) exhibited maximal tyrosinase activity during the 24 h exposure to the melanotropins. Therefore, tyrosinase activity was primarily affected by cell density rather than by the duration of time the cells were in culture or by continuous exposure to melanotropin. Other flasks of various cell densities were treated with 10(-7) M alpha-MSH or [Nle4, D-Phe7]-alpha-MSH for 24 h, followed by removal of the melanotropins from the culture medium. The magnitude and duration of the residual stimulation of melanoma tyrosinase activity by melanotropins were also found to be dependent on the initial cell density. These results reveal that there is a limited range of optimal cell densities at which melanoma cells can respond to melanotropins and express increased tyrosinase activity.
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PMID:Long-term and residual melanotropin-stimulated tyrosinase activity in S91 melanoma cells is density dependent. 308 84

Ac-[Nle4, D-Phe7]-alpha-MSH4-9-NH2 and Ac-[Nle4]-alpha-MSH4-9-NH2, fragment analogs of the tridecapeptide, alpha-melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin), were synthesized. The potency and prolonged activity of the analogs were compared to alpha-MSH in several melanotropin bioassays. The D-Phe-containing hexapeptide was 10 times more active than alpha-MSH in stimulating melanoma tyrosinase activity. This analog was also 10-fold more potent than alpha-MSH in the lizard skin bioassay and about 10-fold less active in the frog skin bioassay. The melanotropic activity of Ac-[Nle4, D-Phe7]-alpha-MSH4-9-NH2 was considerably prolonged compared to alpha-MSH in each of the bioassays. These results demonstrate that the structural requirements for superpotency and prolonged activity of [Nle4, D-Phe7]-substituted analogs reside within this hexapeptide sequence.
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PMID:Potent and prolonged melanotropic activities of the alpha-MSH fragment analog, Ac-[Nle4,D-Phe7]-alpha-MSH4-9-NH2. 308 18

The alpha-MSH (alpha-melanocyte-stimulating hormone) agonist, Ac-[Nle4, D-Phe7]alpha-MSH4-11NH2 (hereafter called ND4-11 alpha-MSH), is at least 10-fold more potent than alpha-MSH as a stimulus of tyrosinase activity in F1 variant cells of B16 melanoma. The binding to these cells during an incubation with 5 nM (3H)ND4-11 alpha-MSH at 37 degrees C is maximal at 0-30 min, 22 fmol/10(6) cells, but declines to 40% of this value at 4 hr. in the presence of 5 nM (3H)ND4-11 alpha-MSH at 37 degrees C, the acid soluble (cell surface) radioactivity decreased rapidly from 11.4 fmol/10(6) cells at 5 min to 4.6 fmol/10(6) cells at 4 hr. Chromatographic analysis of media and cellular samples revealed that there was no evidence of degradation of (3H)ND4-11 alpha-MSH in the medium but there was evidence of intracellular degradation of (3H)ND4-11 alpha-MSH. Ammonium chloride (10mM) resulted in an increase in acid resistant radioactivity (internalized hormone) at 4 hr. The binding to F1 variant cells during an incubation with 0.155 nM or 5 nM (3H)ND4-11 alpha-MSH at 4 degrees C was constant from 4 hr to 24 hr. Under these conditions, there was no time-dependent change in the acid soluble radioactivity from 4 to 24 hr. Scatchard analysis of (3H)ND4-11 alpha-MSH binding to F1 variant cells at 4 degrees C demonstrated that there were approximately 4500 receptors per cell and an association constant of 17.1 nM-1. These results are consistent with a process of (3H)ND4-11 alpha-MSH binding to its receptor followed by internalization of the receptor-hormone complex and then intracellular degradation of the hormone.
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PMID:Biological activity, binding, and metabolic fate of Ac-[Nle4, D-Phe7]alpha-MSH4-11NH2 with the F1 variant of B16 melanoma cells. 311 Jan 78


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