Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0596263 (carcinogenesis)
64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To search for possible anti-tumor-promoters, fourteen flavones obtained from the root of Scutellaria baicalensis were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Among these flavones, 5,7,2'-trihydroxy- and 5,7,2',3'-tetrahydroxyflavone showed remarkable inhibitory effects on the EBV-EA activation, and the effect of the latter on Raji cell cycle was also examined by flow cytometer. These two flavones exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.
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PMID:Studies on inhibitors of skin tumor promotion. XI. Inhibitory effects of flavonoids from Scutellaria baicalensis on Epstein-Barr virus activation and their anti-tumor-promoting activities. 131 92

Squalene inhibited the effect of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), such as increased 32Pi incorporation into phospholipids of HeLa cell membrane, induction of Epstein-Barr-virus early antigen in Raji cell and induction of ornithine decarboxylase in mouse skin. Squalene also markedly suppressed the promoting activity of TPA on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice.
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PMID:Inhibition by squalene of the tumor-promoting activity of 12-O-tetradecanoylphorbol-13-acetate in mouse-skin carcinogenesis. 133 56

Staurosporine, which is a potent inhibitor of protein kinases, such as protein kinase C, inhibited both inductions of adhesion of human promyelocytic leukemia cells (50% effective dose = 9.0 nM) and Epstein-Barr virus early antigen in Raji cells (50% effective dose = 3.4 nM) by teleocidin. However, staurosporine induced irritation on mouse ear and histidine decarboxylase activity in mouse skin. It did not induce ornithine decarboxylase activity in mouse epidermis. The two-stage carcinogenesis experiments of staurosporine were carried out at two different doses. Experiment 1 revealed that the group treatment with a single application of 100 micrograms of 7,12-dimethylbenz(a)anthracene, followed by repeated applications of 50 micrograms of staurosporine, resulted in 85.7% of tumor-bearing mice at Wk 30, whereas group treatment with staurosporine alone or 7,12-dimethylbenz(a)anthracene alone gave 6.7% and 0%, respectively. Experiment 2 showed that group treatment with 7,12-dimethylbenz(a)anthracene followed by applications of 10 micrograms of staurosporine resulted in 33% of tumor-bearing mice at Wk 30. In addition, staurosporine treatment reduced the percentages of tumor-bearing mice treated with teleocidin from 100% to 67% in Wk 15. These results demonstrated that staurosporine is a weak tumor promoter of mouse skin compared with teleocidin, but staurosporine has some potency to inhibit tumor promotion by teleocidin.
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PMID:Tumor-promoting activity of staurosporine, a protein kinase inhibitor on mouse skin. 216 51

A large number of human tumor cell lines of various origins have been investigated with respect to expression of glutathione-linked enzymes in the cytosol fraction. The amounts of the different enzymes were estimated by use of activity measurements and by silver staining or immunoblot analysis after electrophoresis of cytosol fractions purified by affinity chromatography on S-hexylglutathione Sepharose. Class Pi glutathione transferase was the most abundant enzyme in most tumor cells; the cell lines HepG2 and Raji were exceptions in not expressing significant amounts of this enzyme. HepG2 cells derive from hepatocytes, which normally do not express the class Pi enzyme, whereas Raji cells originate from B-lymphocytes, which normally do express a class Pi glutathione transferase. The highest level of the class Pi transferase, in terms of protein reacting with antibodies as well as enzyme activity, was noted in the colon carcinoma cell line LS174T. Hu549Pat cells, EBV-transformed B-lymphocytes, also expressed high levels of a protein reacting with antibodies specific for class Pi glutathione transferases, but did not display any significant activity with ethacrynic acid, a substrate characteristic for this class. Class Alpha and class Mu glutathione transferases, in cell lines expressing these isoenzymes, were present in significantly lower concentrations than the class Pi enzyme. Most of the tumor cells contained a class Alpha transferase composed of 27.5 kd subunits, which has the physicochemical and immunological properties of the most basic glutathione transferase found in human skin. In several cell lines, a protein was detected with an apparent subunit Mr value of 30 kd that was tentatively identified as an additional class Alpha glutathione transferase not previously described. In addition, other glutathione-linked enzyme activities, namely glutathione peroxidase, glutathione reductase and glyoxalase I, were assayed with specific substrates in the cytosolic fraction of the tumor cells; glyoxalase I could also be estimated semiquantitatively by silver staining of SDS-PAGE cells after affinity chromatography. Like the glutathione transferases, these enzymes displayed distinctly different levels of expression in the various cell lines. Thus, virtually every cell line was found to have a unique pattern of glutathione-linked enzymes, suggesting that the resistance phenotypes of the cells differ accordingly.
Carcinogenesis 1990 Sep
PMID:Differences among human tumor cell lines in the expression of glutathione transferases and other glutathione-linked enzymes. 240 Oct 46

The macrocyclic lactone bryostatin 1 activates protein kinase C as effectively as the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Nevertheless, there are only certain TPA-effects that can be induced by bryostatin 1. These include stimulation of epidermal DNA synthesis and alkaline phosphatase activity in vivo as well as activation of the Ca2+-independent, phospholipid-requiring phosphorylation of an epidermal protein in a cell-free system. Various other TPA-effects in vivo and in vitro, which are not mimicked by bryostatin 1 can be inhibited by applying bryostatin 1 30 min prior to TPA. TPA-effects suppressible by bryostatin 1 include the Ca2+-dependent stimulation of arachidonic acid and prostaglandin E2 release, of ornithine decarboxylase (ODC) activity and ODC-mRNA expression and of transglutaminase activity in keratinocytes in vivo and/or in vitro and, in addition, Epstein-Barr virus induction in Raji cells. The same is true for the conversion step (first stage of promotion) of multistage carcinogenesis. In contrast to the TPA induction of arachidonic acid and prostaglandin E2 release and of transglutaminase activity, induction by the Ca2+-ionophore and by high Ca2+-shift, respectively, are not significantly inhibited by bryostatin 1. We suggest that bryostatin 1 might inhibit a specific 'Ca2+-component' of TPA action.
Carcinogenesis 1988 Apr
PMID:Bryostatin 1, an activator of protein kinase C, mimics as well as inhibits biological effects of the phorbol ester TPA in vivo and in vitro. 245 75

Epstein-Barr virus (EBV) activation of latent infection and traditional life styles, especially food habits, have been strongly associated with an increased risk of nasopharyngeal carcinoma (NPC) in humans. On the basis of anthropological studies in Tunisia, southern China and Greenland, extracts of representative preserved food items consumed frequently by the high-risk populations for NPC were assayed for the presence of EBV activators in Raji cells. A strong EBV activation activity was observed in aqueous extracts of some Cantonese salted dried fish from China, harissa (a spice mixture) and to a lesser extent qaddid (dry mutton preserved in olive oil) from Tunisia. These new data may support epidemiological evidence for the importance of Cantonese salted and dried fish and other food items in the etiology of NPC.
Carcinogenesis 1988 Aug
PMID:Epstein-Barr virus activation in Raji cells by extracts of preserved food from high risk areas for nasopharyngeal carcinoma. 284 Oct 48

Cigarette smoke condensate (CSC) was separated into several fractions and each was tested for an inhibitory effect on the early antigen (EA) of Epstein-Barr virus (EBV) which can be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Two diastereoisomers of 2,7,11-cembratriene-4,6-diol (alpha- and beta-CBT) were isolated from the neutral fractions of CSC and these showed potent inhibitory effects on the induction of EBV-EA by TPA. The doses of alpha- and beta-CBT required for 50% inhibition of EBV-EA induction by TPA were 7.7 and 6.7 micrograms/ml, respectively, which are comparable with those of retinoic acid, a potent inhibitor of induction of epidermal ornithine decarboxylase (ODC) activity and tumor promotion by TPA in mice. Application of alpha- and beta-CBT to mouse skin prior to treatment with TPA inhibited TPA-induced ODC activity. The degree of inhibition was dependent on the dose and application of 16.5 mumol/mouse of alpha- and beta-CBT resulted in a 50 and 40% reduction, respectively, of the maximum of the ODC activity induced as a result of treatment with TPA. In initiation-promotion experiments, alpha-CBT markedly inhibited the promoting effect of TPA on skin tumor formation in mice which were initiated with 7,12-dimethylbenz[a]anthracene, but beta-CBT was found to be less effective. Application of 3.3 mumol of alpha-CBT 40 min prior to treatment with TPA (1 microgram) resulted in a 53% reduction in the number of papillomas per mouse. Our present data suggest that EBV-EA inhibition assay using Raji cells is effective for the first screening of inhibitors of tumor promotion, and provide evidence that CSC contains antitumor-promoting agents in addition to carcinogenic and tumor-promoting agents already reported.
Carcinogenesis 1985 Aug
PMID:Identification of cembratriene-4,6-diol as antitumor-promoting agent from cigarette smoke condensate. 299 Jul 57

Upon stimulation with a phorbol ester and known tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), the human erythroleukemia K562 cell line, a standard target for human natural killer (NK) cells, shows a significant reduction in expression of transferrin receptors (TfR) and becomes resistant to NK-mediated cytolysis. Prompted by the initial finding that expression of TfRs by K562 cells correlates with target sensitivity to NK cytotoxicity, we have investigated the role of two proposed NK-target structures, the TfR and 4F2 molecule in three other tumour cell lines which vary in their susceptibility to NK activity. We report that similar to K562 cells, MOLT 4, Raji and HL60 cells demonstrate phorbol-ester-induced down-regulation of TfR expression. The expression of TfRs alone does not determine target sensitivity. However, TfRs are probably located close to the NK-target structure in NK-sensitive cell lines. Based on the properties of phorbol ester induction, it is possible that the NK-target molecule is down-regulated in response to phorbol ester induction in a similar, if not identical manner to that of the TfR; thus, rendering NK-sensitive cells resistant to NK killing, after TPA exposure. Conversely, the target molecule is probably upregulated in MOLT 4 cells after TPA treatment as indicated by the acquired sensitivity of these cells to NK-mediated cytolysis. The expression of 4F2 molecules was not influenced by TPA treatment and does not correlate with NK sensitivity.
Carcinogenesis 1988 Aug
PMID:Transferrin receptor and 4F2 expression by NK-sensitive and NK-resistant tumour cell lines. 316 9

A Simian virus 40-driven shuttle vector plasmid (pZ189) was treated with 8-methoxypsoralen plus a split dose of long-wavelength UV (UVA) radiation in order for a large number of psoralen cross-links, as compared with monoadducts, to be formed in the plasmid DNA. The shuttle vector was then transfected into monkey Vero or human Raji cells. Plasmids replicated in the primate host cell were extracted 2 days later and analysed for mutations in the vector suppressor tRNA (supF) gene. A spontaneous mutation frequency of 0.7 X 10(-3) was 15-fold elevated in vectors exposed to psoralen plus two UVA irradiations. Most of these mutations were considered to be dependent on DNA cross-link adducts, since psoralen plus only a single UVA dose (producing mainly monoadducts) did not appreciably affect the mutation rate. DNA sequence analysis revealed a hot spot at an AT repeat constituting a potential site for psoralen cross-link formation, whereas the second hot spot noted did not contain any sequence where psoralen adduct formation is likely to occur. Since the AT repeat hot spot was not represented in previous studies with pZ189 exposed to other genotoxic agents, the results indicate that a specific mutational pattern may be resulting from induction of DNA cross-links.
Carcinogenesis 1987 Dec
PMID:Psoralen adducts in a shuttle vector plasmid propagated in primate cells: high mutagenicity of DNA cross-links. 367 15

The Burkitt's lymphoma cell line Raji has a Mex+ phenotype. It is more resistant to killing by alkylating agents than a sub line (Raji TK-) which is Mex-. A reduction in O6-methylguanine (O6MeG)-DNA methyltransferase can be brought about by growing Raji cells in the presence of free O6MeG. The depletion in enzyme activity is specific and reversible; removal of O6MeG from the medium results in the restoration of methyltransferase activity within 4 h. Raji cells, in which methyltransferase has been reduced by this treatment to below detectable levels, are not sensitised to killing by N-methyl-N'-nitro-N-nitrosoguanidine or the cross-linking nitrosoureas, 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-1-nitrosourea. This implies that adducts at the O6 atom of guanine in DNA are not potentially cytotoxic lesions. Secondly, it suggests that a defect other than the lack of methyltransferase is responsible for the sensitivity of Mex- cells to killing by alkylating agents.
Carcinogenesis 1985 May
PMID:The cytotoxic and mutagenic effects of alkylating agents on human lymphoid cells are caused by different DNA lesions. 400 64


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