Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoic acid was found to be a potent stimulant of pigmentation in human Hs939 melanoma cells. Exposure to 1 microM retinoic acid for longer than four days caused both a decrease in the rate of cell proliferation and a concomitant increase in melanogenesis. These effects of retinoic acid progressed lin-early in a time-dependent and a dose-dependent fashion such that at the end of a seven-day treatment cell growth was inhibited by approximately 65%, and both melanin content and tyrosinase activity increased more than three-fold over the control. Interpolation of the dose-response curves indicated that 3 nM retinoic acid would cause half-maximal melanogenesis stimulation. No elevation in the level of cyclic adenosine 3':5'-monophosphate could be detected in the melanoma cells following various periods of exposure to retinoic acid, and the cells were unresponsive to alpha-melanocyte-stimulating hormone. In the presence of the tyrosinase inhibitor phenylthiocarbamate, retinoic acid was capable of inhibiting cell proliferation without enhancing melanin synthesis. The tumor promoter phorbol myristate acetate did not affect either the proliferation or the differentiation of the Hs939 melanoma cells. However, the enhancement of melanogenesis by 1 microM retinoic acid was inhibited by 66% in the presence of 0.1 microM phorbol myristate acetate. The tumor promoter did not reverse the growth-inhibitory effect of retinoic acid. Phorbol, a non-tumor promoter, was effective. Other retinoids, such as 13-cis-retinoic acid, retinyl acetate, nd the trimethylmethoxyphenyl analog of retinoic acid, also inhibited the proliferation and enhanced melanin production in the Hs939 cells. In contrast, retinyl palmitate, the phenyl analog of retinoic acid, and the pyridyl analog of retinoic acid were ineffective.
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PMID:Stimulation of melanogenesis in a human melanoma cell line by retinoids. 625 61

The acute in vitro actions of two potent melanocytolytic agents, hydroquinone (HQ) and beta-mercaptoethanolamine (MEA), were determined in the B-16, Cloudman S-91 and Harding-Passey (HP) murine melanomas grown in vivo. Drug treated melanoma dice (5--480 min) were analyzed for tyrosinase activity and cyclic nucleotide levels (cAMP, cGMP). HQ and MEA effects on tyrosinase activity are complex and vary with tumor type, duration of treatment and agent tested. MEA or HQ inhibited B-16 tyrosinase activity. With combined drug therapy, low concentrations of MEA plus HQ stimulate B-16 tyrosinase activity while high concentrations of the drugs have little effect on enzymatic activity. MEA depresses tyrosinase activity while HQ elevates enzymatic activity in the S-19 melanoma. Both high and low concentrations of the combined drugs (MEA plus HQ) elicit the same response, stimulation at 10 min followed by continued depression of tyrosinase activity for the remainder of the 4 h study period. MEA initially stimulates HP tyrosinase activity followed by depression of enzymic activity. In contrast, HQ initially depresses HP tyrosinase activity followed by stimulation of enzyme activity. In combination the drugs inhibit HP tyrosinase activity. The effects of MEA and/or HQ on murine melanoma cyclic nucleotide levels are equally complex. MEA or HQ elevate cAMP and cGMP levels in all three tumors with the exception of S-91 cGMP levels which are not altered. In combination the drugs increase cyclic nucleotide levels in each of the three tumor types but at different times. No correlation is present between cyclic nucleotide levels and tyrosinase activity. Thus, the action of increased cyclic nucleotide levels in melanogenesis can not be separated from the direct actions of MEA and HQ upon melanogenesis. The divergent effects of MEA and/or HQ on tyrosinase activity and cyclic nucleotide levels in these melanomas are not correlated with the known in vivo melanocytolytic activity of these drugs. Thus, these parameters appear to be inadequate indicators of melanoma cell viability in chemotherapeutic screening of drugs effective in destroying malignant melanoma.
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PMID:Acute effects of two melanocytolytic agents, hydroquinone and beta-mercaptoethanolamine, upon tyrosinase activity and cyclic nucleotide levels in murine melanomas. 625 89

Retinoic acid (RA), which reduces the rate of cell proliferation in S91 mouse melanoma clone C2 cells, was found to stimulate the expression of their melanotic phenotype. RA treatment also induced the extension of long cellular processes. The RA effects on melanogenesis included stimulation of tyrosinase activity and augmentation of cellular melanin content to levels 3- to 4-fold higher than in untreated cultures at similar cell densities. These effects became apparent after 48 hours of exposure to 10(-5) M RA and increased thereafter. Half-maximal stimulation in cells treated for 6 days occurred at 5 X 10(-7) M RA. Although the degrees of melanogenesis enhancement by RA (10(-5) M) and by alpha-melanocyte stimulatory hormone (2 X 10(-7) M) were similar, the former did not alter the intracellular cAMP level, whereas the latter induced a transient 4-fold increase. In high-passage (p28) cells, as well as in low-passage cells (less than p10) treated with tyrosinase inhibitor phenylthiocarbamate, melanin synthesis was suppressed in the absence and presence of RA, yet the ability of RA to inhibit cell proliferation was not compromised. In the presence of the tumor promotor phorbol myristate acetate (greater than 5 X 10(-9) M) melanin synthesis in control as well as in cells exposed to RA was dramatically inhibited. Phorbol which is not active in tumor promotion had no effect on melanogenesis. In addition to RA, other retinoids, such as 13-cis-retinoic acid, retinyl acetate, the TMMP analog of RA and the phenyl analog of RA, but not the pyridyl analog of RA or retinyl palmitate, also inhibited cell growth and enhanced melanin synthesis.
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PMID:Enhancement of melanotic expression in cultured mouse melanoma cells by retinoids. 626 Aug 17

The level of cAMP was investigated in the following three types of hamster malignant melanomas: amelanotic, depigmented and melanotic. The amelanotic and depigmented tumors were undifferentiated, with high proliferative activity, and lacked tyrosinase. The melanotic one was slow growing, highly differentiated, and expressed tyrosinase activity. Among the melanomas investigated, the higher concentration of cAMP was found in undifferentiated tumors. The single treatment of the tumor-bearing animals with theophyllin or isoproterenol did not change the cAMP level in melanotic tumors, but significantly enhanced the cAMP content in amelanotic and especially depigmented melanomas. Multiple theophyllin treatment of tumor-bearing animals caused elevation of cAMP content in all tumors, but this effect was accompanied by enhancement of tyrosinase activity only in melanotic melanoma.
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PMID:Effect of theophyllin and isoproterenol on cAMP level in melanotic and amelanotic hamster melanomas. 631 98

An exposure of cultured Cloudman S91 melanoma cells to inhibitors of polyamine biosynthesis, 2-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG), distinctly promoted the expression of differentiated biochemical functions of the tumor cells. Slight to moderate growth inhibition produced by the compounds was associated with a stimulation of melanogenesis, as reflected by a striking enhancement of tyrosinase (EC 1.10.3.1) activity and an increase in cellular melanin content. Both antimetabolites acted synergistically with alpha-melanotropin (MSH), as regards the stimulation of melanogenesis. Exposure of the melanoma cells to MSH resulted in most experiments in a marked decrease of the intracellular polyamine pools, usually involving all three polyamines (putrescine, spermidine and spermine). The DFMO-induced stimulation of melanogenesis was totally suppressed by the administration of putrescine, whereas the MSH-stimulated tyrosinase activity was not influenced by the diamine. Although many recent reports indicate that terminal differentiation is accompanied by a distinct stimulation of polyamine biosynthesis, our results suggest that in certain cells polyamine deprivation may lead to an enhanced expression of differentiated phenotype.
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PMID:Stimulation of melanotic expression in murine melanoma cells exposed to polyamine antimetabolites. 640 78

The transfer of tyrosinase from microsomes into melanosomes, without passing through the cytosol in the Harding-Passey mouse melanoma cell, was confirmed by experiments carried out using a combination of radioisotope tracer techniques and immunoprecipitation. 3H-Labeled amino acid incorporation into tyrosinase present in the microsome, melanosome, and soluble fractions confirmed the precursor-product relationship of the enzyme in the microsome fraction and in the melanosome fraction. However, two forms of the enzyme, Ts1- and Ts2-tyrosinase, separated from the soluble fraction by polyacrylamide gel electrophoresis, were shown to play no role in the transfer since little or no incorporation of radioactivity into tyrosinase in this fraction was found. It is suggested that most tyrosinase observed in the soluble fraction does not leak from the melanosomes or the microsomes during homogenization, but comes from necrotic tumor cells. It appears that melanosomal and microsomal tyrosinase might be released from the membrane of necrotic cells modified by various degradation enzymes, considering the data on the recovery of tyrosinase from the soluble fraction, where one-third of total enzyme activity in the postnuclear fraction could not be increased, even when the postnuclear fraction of the tumor was further homogenized radically.
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PMID:Transfer of tyrosinase to melanosomes in Harding-Passey mouse melanoma. 641 34

The production of 5-S-cysteinyldopa by a newly established melanoma cell line GAK is reported. The cell line was derived from a metastatic inguinal lymph node of vulvar malignant melanoma. The cell line grew well without interruption for over 4 years, GAK cells were proved to have melanin granules and tyrosinase activity in their cytoplasma by Masson's staining and dopa reaction, respectively. Melanin granules were ultrastructually identified as melanosomes in various maturing stages. The chromosomal number varied widely and showed aneuploidly, but the modal chromosomal number was stable in the hypotriploid range. GAK cells were transplanted to nude mice and produced tumors resembling the original. Because glucose-6-phosphate dehydrogenase of GAK revealed a type B (slow) mobility pattern on electrophoresis, the possibility of Hela cell contamination could be completely excluded. High performance liquid chromatography revealed "5-S-cysteinyldopa", a new tumor marker of malignant melanoma, in culture media of GAK cells. The cell line described may serve as a representative model system for basic and clinical studies on malignant melanoma.
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PMID:[A newly established melanoma cell line (GAK) with 5-S-cysteinyldopa phenotype]. 643 Oct 36

Selection of the most melanized tissue of the slightly melanotic MI melanoma in hamster resulted in an origin of a new highly melanotic tumor line. It differed from the parental MI melanoma in the 5-fold higher melanin content, but its tyrosinase activity, growth rate and histological structure remained unchanged. Selection of the least melanotic tissue of the MI melanoma did not give positive results.
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PMID:Effect of tissue selection on melanization of MI hamster melanoma. 643 37

Levodopa and dopamine are naturally occurring catecholamines with antitumor activity in several experimental tumor systems. Previous studies suggested that their cytotoxic effect was related in part to their inhibitory effect upon DNA polymerase. We have examined the effects of levodopa, dopamine, levodopa methyl ester, norepinephrine, and the analog 3,4-dihydroxybenzylamine upon human and murine melanoma cells. When exponentially growing cells were exposed to these drugs, a characteristic inhibition of thymidine incorporation was observed with much less inhibition of either uridine or leucine incorporation. In order to ascertain that inhibition was occurring at the level of DNA synthesis, we examined the effects of the drugs upon the incorporation of thymidine triphosphate by permeabilized melanoma cells. When melanoma cells were permeabilized by lysolecithin, thereby permitting the direct incorporation of labeled thymidine triphosphate, a similar inhibition of incorporation was observed. Dopamine at a concentration of 4.8 microM caused a 50% reduction in incorporation of label. These results suggested that inhibition did occur at the level of DNA synthesis. In the presence of the melanocyte-specific oxidase, tyrosinase, these derivatives are potent inhibitors of isolated DNA polymerase alpha with 50% inhibitory concentrations between 1 and 10 microM. The inhibition could be completely prevented by the presence of reducing agents such as dithiothreitol (1.0 mM). The quinols themselves were not inhibitors of DNA polymerase. Dopamine analogs represent an interesting class of antitumor agents with inhibitory activity for DNA polymerase.
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PMID:Levodopa and dopamine analogs as DNA polymerase inhibitors and antitumor agents in human melanoma. 676 47

A fish melanoma cell line, PSM-1, was established from a hereditary melanoma in an interspecific hybrid of Xiphophorus for cytogenetic studies of this melanoma system. An amelanotic melanoma was obtained from the tail fin of a melanotic F1 hybrid between a spotted platyfish (Xiphophorus maculatus) and an albino swordtail (Xiphophorus helleri). The tumor tissue was dissociated and cultured in Eagle's minimal essential medium supplemented with 10% fetal calf serum. PSM-1 has been maintained for 52 passages and 29 months in vitro since March 3, 1978. This cell line showed considerable variation in cellular morphology. Although no apparent pigment was detectable by light microscopy, melanosomes and premelanosomes could be seen under the electron microscope. The cells grew randomly across each other with an apparent lack of contact inhibition and formed many clumps. The doubling time was approximately 2 days, and the modal chromosome number at the 41st passage was a near triploid 71. A high tyrosinase activity was detected. PSM-1 is similar to some mammalian melanoma cell lines with respect to cytological characteristics and growth patterns.
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PMID:Establishment of a cell line from the platyfish-swordtail hybrid melanoma. 677 12


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