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 in vitro proliferation of murine melanoma cell lines S91 and B16 was inhibited by retinoic acid and retinyl acetate. The inhibitory effects were dependent on retinoid concentration and increased from 55 and 30% at 10(-9) M retinoic acid to 85 and 82% at 10(-5) M retinoic acid for S91 and B16 melanoma cells, respectively. S91 melanoma cells were more sensitive than B16 melanoma cells to inhibition by either retinoid, and both cell lines were more sensitive to retinoic acid than to retinyl acetate. When exposed to 10(-5) M retinoic acid, the two cell types grew at the same rate as did control cells for 48 hours, whereupon the growth rates of retinoid-treated cells decreased. After 6 days, the number of cells in control cultures increased 140 times (S91 melanoma cells) and 265 times (B16 melanoma cells), whereas retinoic acid-treated cells increased only 14 times (S91 melanoma cells) and 40 times (B16 melanoma cells). The degree of growth inhibition by retinoic acid was not dependent on initial cell density. Cortisone and hydrocortisone failed to prevent or reduce the inhibitory effect of retinoic acid; the release of lysosomal acid phosphatase was not increased and the intracellular level of 3',5'-cyclic AMP in cells grown for 5 days in the presence of 10(-5) M retinoic acid was not elevated. Viability of S91 and B16 cells after 8 days' exposure to 10(-5) M retinoic acid was similar to that in control cultures. The reduced growth rate of retinoic acid-treated cells reversed to the control rate 48-72 hours after removal of retinoic acid from the growth medium.
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PMID:Characterization of the inhibitory effects of retinoids on the in vitro growth of two malignant murine melanomas. 20 60

Screening for retinoic acid-binding protein (RABP) in experimental tumors revealed the presence of this protein in three mammary tumors, two metastatic colon tumors, B16 melanoma. Lewis lung carcinoma, Ridgway osteogenic sarcoma, and keratoacanthoma. RABP was below the limits of detection in two weakly metastatic colon tumors and in Sarcoma 180. After s.c. implantation of RABP-containing tumors into mice, this protein could be traced in the lungs due to pulmonary metastasis. Following implantation of Lewis lung tumors, RABP was detected in the lung on the 6th day. On the 15th day after implantation, RABP was present in lung and brain, but not in other tissues where this protein was normally lacking. In primary cultures of Lewis lung carcinoma, the lower limit for detection of RABP by sucrose gradient sedimentation technique corresponded to 0.12 mg protein that was extractable from 3 X 10(5) cells. Both chick embryo skin and rabbit ear skin extracts contained RABP; the level of cellular retinol-binding protein was high in chick embryo skin but only marginal in rabbit ear. The amounts of these proteins on chick embryo skin and rabbit ear skin correlate with the biological potency of retinol and retinoic acid, as observed by others.
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PMID:Retinoic acid-binding protein in experimental tumors and in tissues with metastatic tumor foci. 56 58

The active component of the honeybee hive product propolis, caffeic acid phenethyl ester (CAPE), has been shown to display increased toxicity toward various oncogene-transformed cell lines in comparison with their untransformed counterparts (Su et al., 4: 231-242, 1991). This observation provides support for the concept that it is the transformed phenotype which is specifically sensitive to CAPE. In the present study, we have determined the effect of CAPE on the growth and antigenic phenotype of a human melanoma cell line, HO-1, and a human glioblastoma multiforme cell line, GBM-18. For comparison, we have also tested the effects of mezerein (MEZ), mycophenolic acid (MPA) and retinoic acid (RA), which can differentially modulate growth, differentiation and the antigenic phenotype in these human tumor cell lines. Growth of both cell lines was suppressed by CAPE in a dose-dependent fashion, with HO-1 cells being more sensitive than GBM-18 cells. The antiproliferative effect of CAPE was enhanced in both cell types if CAPE and MEZ were used in combination. Growth suppression was associated with morphological changes in H0-1 cells, suggesting induction of a more differentiated phenotype. CAPE also differentially modulated the expression of several antigens on the surface of the two tumor cell lines. These results suggest a potential role for CAPE as an antitumor agent, an antigenic modulating agent and possibly a differentiation inducing agent.
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PMID:Growth inhibition and modulation of antigenic phenotype in human melanoma and glioblastoma multiforme cells by caffeic acid phenethyl ester (CAPE) 128 53

Xeroderma pigmentosum is a rare recessive disease with sun sensitivity, increased freckling and defective DNA repair. Xeroderma pigmentosum patients have more than a 1000-fold increased risk of developing skin cancer including basal cell carcinoma, squamous cell carcinoma and melanoma. We studied chemoprevention of new skin cancers with oral retinoids in xeroderma pigmentosum patients who had multiple skin cancers. Xeroderma pigmentosum patients were cleared of all pre-existing tumors surgically and then treated with high dose (2 mg/kg/day) oral isotretinoin (13-cis retinoic acid, Accutane) for two years and then for one year off treatment. Patients were examined at regular intervals for new tumor formation and for side effects. Five xeroderma pigmentosum patients had a total of 121 basal or squamous cell carcinomas in 2 years before treatment and only 25 tumors during 2 years of treatment. The tumor frequency increased 8.5-fold after the drug was discontinued (New Engl J Med 318: 1633-1637, 1988). Toxicity (cutaneous, triglyceride, liver-function or skeletal abnormalities) prompted subsequent use of a low dose protocol. Patients were treated initially with 0.5 mg/kg/day oral isotretinoin and the dose was increased sequentially to 1.0 or 1.5 mg/kg/day. We found that toxicity was less with the lower doses. The lowest effective, least toxic dose varied among the xeroderma pigmentosum patients.
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PMID:Chemoprevention of skin cancer in xeroderma pigmentosum. 129 59

beta-All-trans-retinoic acid (RA) has been shown to inhibit the growth, enhance the differentiation, and suppress the transformed and metastatic properties of certain human and murine melanoma cells. This study examined the effect of RA on the level of a cell surface receptor (M(r) 78,000) (gp78) for an autocrine motility factor, which has been implicated in invasion and metastasis. Treatment of murine melanoma cell lines S91-C2, B16-F1, and K1735-P with RA (10 microM) for 5 days decreased the level of gp78 by 37, 72, and 92%, respectively, as revealed by immunoblotting with monoclonal antibodies raised against gp78. In contrast, RA had only a limited effect on gp78 levels in melanoma cell clones or variant cell lines that are resistant to the growth-inhibitory effects of RA (S91-C154, B16-F10, and K1735-Cl19). Further studies with K1735-P, the most sensitive cell line with respect to modulation of gp78, showed that the decrease in gp78 level required at least 1 microM RA and 4 to 5 days of treatment. The binding of anti-gp78 antibodies to the surface of intact RA-treated cells and to intracellular gp78 in permeabilized cells was also lower than in untreated cells. Furthermore, RA treatment decreased the induction of cell motility, on colloidal gold-coated glass coverslips, by anti-gp78 antibodies, which mimic the effect of autocrine motility factor. The RA-induced decrease in antibody-enhanced cell motility was similar to the time- and RA concentration-dependent decrease in the amount of gp78, suggesting that the two events are related. These results raise the possibility that the previously reported suppression by RA of tumor cell invasion and metastasis may be related, at least in part, to suppression of cell motility resulting from the decreased level of the autocrine motility factor receptor.
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PMID:Suppression of melanoma cell motility factor receptor expression by retinoic acid. 132 86

The differentiation-inducing activity of doxorubicin on B16 melanoma cells grown in vitro was compared with that of other known differentiation inducers, such as theophylline, retinoic acid, and melanocyte-stimulating hormone (MSH). At drug concentrations resulting in cytostatic effects, doxorubicin and theophylline induced morphological changes (dendritic-like structures with a terminal melanin granule) with an enhancement of total melanin content and tyrosinase activity. Retinoic acid did not alter melanin content and cell morphology, although it affected cell growth. MSH enhanced total melanin content and tyrosinase activity, with no significant morphological changes. Flow cytometric analysis showed that MSH led to an accumulation of cells in G1 phase whereas doxorubicin induced an accumulation of cells in G2 + M. Studies on DNA content in doxorubicin-treated cells, selected on the basis of a morphologically differentiated pattern, showed a clustering of these cells in G2 + M, probably due to a cytokinesis block. Thus doxorubicin can induce cell differentiation comparable with other differentiation inducers.
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PMID:Comparative studies on the effects of doxorubicin and differentiation inducing agents on B16 melanoma cells. 132 7

Topical tretinoin improves mottling and hyperpigmented lesions of photodamaged skin. The basic mechanisms underlying these effects are not known. It is demonstrated that retinoids inhibit the growth and enhance the differentiation of melanoma cells in vitro, and stimulate the constitutive melanogenesis in melanoma cells in vitro. On the other hand, they inhibit hormonally or pharmacologically induced melanogenesis in these cells. Very few data are available concerning the effect of retinoic acid on normal human melanocytes, but there is some inhibition of growth as in melanoma cells. Retinoic acid appears to have little effect on the melanogenesis of normal human melanocytes grown in vitro using serum-free culture medium. Changes in the shape of these melanocytes suggest that retinoic acid acts on cytoskeleton proteins. Further studies, both in vitro and in vivo, are needed to clarify the effects of retinoic acid on melanocytes.
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PMID:Retinoic acid and pigment cells: a review of in-vitro and in-vivo studies. 132 62

alpha-MSH was found to decrease the recently characterized dopachrome tautomerase activity in cultures of B16/F10 mouse melanoma cells. Other stimulating agents of melanogenesis, like dibutyryl cyclic AMP, 3-isobutyl-1-methylxanthine, theophylline, retinol, and retinoic acid, caused the same effect. The grade of inhibition depended on the nature of the agent and the time of exposure. In all cases, both melanin production and tyrosinase activity were activated by these treatments, although the grade of tyrosine hydroxylase and dopa oxidase stimulation was different. Moreover, no correlation among the intensities of dopachrome tautomerase inhibition and tyrosinase activation by the tested agents could be obtained. The significance of these results in the regulation of mammalian melanogenesis is discussed.
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PMID:Alpha-MSH and other melanogenic activators mediate opposite effects on tyrosinase and dopachrome tautomerase in B16/F10 mouse melanoma cells. 132 99

MTS1 is a metastasis-associated gene highly expressed in highly metastatic tumours. NM23 has been described as a putative metastasis suppressor gene. Here we show that thapsigargin (which raises intracellular calcium [Ca2+]i from intracellular stores) and verapamil (which blocks Ca2+ influx) both down-regulate MTS1 and NM23 gene expression in the poorly metastatic F1 and highly metastatic ML8 variants of the B16 murine melanoma without altering their metastatic behaviour. The data presented here suggest that Ca2+ released from intracellular stores could be functionally differentiated from influxed Ca2+ and could be activating different components of the Ca2+ signalling system. Many of the cellular responses to calcium are mediated through calmodulin. We have therefore further investigated the role of Ca2+ in the regulation of the MTS1 and NM23 genes using the calmodulin inhibitor W-7. Both these genes were down-regulated after treatment of the F1 and ML8 cell variants. We have shown previously that retinoic acid reduces lung colonization by the highly metastatic variant ML8 and that melanocyte stimulating hormone (MSH) enhances lung colonization by the poorly metastatic variant F1, with corresponding changes in the relative expression of NM23 and MTS1. Here we have found that verapamil and thapsigargin have no effect on lung colonization, possibly due to both genes being down-regulated. These data support the concept that NM23 and MTS1 gene expression is linked and that metastatic potential may be determined by their relative expression.
Melanoma Res 1992 Dec
PMID:Modulators of intracellular Ca2+ and the calmodulin inhibitor W-7 alter the expression of metastasis-associated genes MTS1 and NM23 in metastatic variants of the B16 murine melanoma. 133 98

The potential role of intercellular adhesion molecule 1 (ICAM-1) in the biology of human melanoma cells has stimulated interest in the characterization of its modulation. The present study has shown that the differentiating agent retinoic acid (RA) up-regulates ICAM-1 expression by melanoma cells in a dose- and time-dependent fashion. The enhancement of ICAM-1 cell surface expression is paralleled by an increase in ICAM-1 mRNA. Therefore, ICAM-1 represents an additional gene which may be transcriptionally regulated by RA. The five melanoma cell lines tested displayed a differential susceptibility to the modulation of ICAM-1 expression by RA, since the cell line MeWo did not change in its ICAM-1 expression following incubation with RA. Nevertheless, RA-insensitive as well as RA-sensitive melanoma cell lines displayed a higher increase in ICAM-1 expression following incubation with RA and cytokines than following incubation with each of them. Analysis of the distribution in the melanoma cell lines of retinoic acid receptors (RARs) showed a relationship between susceptibility to a RA-mediated increase of ICAM-1 expression and RAR beta expression, suggesting that the latter receptor may play a role in the phenomenon. RAR alpha and RAR gamma were present in RA-sensitive and -insensitive melanoma cell lines, suggesting that they play a role in the enhancement by RA of cytokine-mediated up-regulation of ICAM-1 expression. The melanoma cell lines we have described may represent a useful system for investigating the role of RAR in the regulation of gene expression and the mechanism(s) which underlie this effect.
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PMID:Differential susceptibility of cultured human melanoma cell lines to enhancement by retinoic acid of intercellular adhesion molecule 1 expression. 135 9


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