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

The Epstein-Barr virus (EBV) is involved in the carcinogenesis of several human cancers such as nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). Given the consistent role of EBV in transformation and maintenance of malignant phenotype, antiviral strategies provide an attractive approach to target EBV-expressing cells. In that aim, we have tested the Cidofovir, which is an acyclic nucleoside phosphonate analog known to exert an antiproliferative activity in some human virus-related tumors. Here, we show that Cidofovir induces a downregulation of the EBV oncoprotein LMP1 associated with a decrease of the antiapoptotic Bcl-2 and an increase of the proapoptotic Bax protein in Raji (BL) and C15 (NPC) cells. Using BL cell line BL2 B95-8 (BL2 infected with the B95.8 strain of EBV), we addressed the relation between EBV genome expression and modulation of viral oncoproteins by Cidofovir and/or ionizing radiation (IR). Cidofovir was able to significantly reduce LMP1 and EBNA2 mRNA and protein expression. This effect was associated with inhibition of proliferation, stimulation of apoptosis, and decrease of Bcl-2 expression in BL2 B95.8 cells. In addition, Cidofovir enhanced the radiation-induced apoptosis and the radiosensitivity through the proteolytic cleavage of death effectors caspase-9 and -3, which was specifically induced by combined treatment in EBV-positive cells compared to their negative counterparts. Furthermore, the combined treatment in nude mice led to a complete tumor remission without increasing toxicity in two human EBV-related cancer xenografts (Raji and C15). These results provide the basis for a novel anticancer strategy to enhance the therapeutic ratio of IR in EBV-related cancers.
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PMID:Antiviral agent cidofovir decreases Epstein-Barr virus (EBV) oncoproteins and enhances the radiosensitivity in EBV-related malignancies. 1270 Jun 62

Seventeen acridone alkaloids isolated from the Rutaceous plants were tested for their inhibitory activities against Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. Some prenylated acridones were found to have remarkably potent activities. 1,3-Dihydroxy-10-methyl-2,4-diprenylacridone (18) as synthesized according to these results in vitro, exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The result of the present investigation indicated that some of these acridone alkaloids may be potentially valuable cancer chemopreventive agents.
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PMID:Cancer chemopreventive activity of acridone alkaloids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis. 1270 69

A study of the chemical constituents of the stems of Derris trifoliata Lour. (Leguminosae) led to the isolation and identification of one new rotenoid, 6aalpha,12aalpha-12a-hydroxyelliptone ( 3), together with five other known rotenoids. In a search for novel cancer chemopreventive agents (anti-tumor promoters), we carried out a primary screening of five of the rotenoids isolated from the plant for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. The inhibitory activity of 3 was found to be equivalent to that of beta-carotene without any cytotoxicity. Deguelin ( 4) and alpha-toxicarol ( 5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that rotenoids might be valuable anti-tumor promoters.
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PMID:Cancer chemopreventive activity of rotenoids from Derris trifoliata. 1522 12

The inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in Raji cells as a primary screening test for anti-tumor promoters, for 22 fatty acids (as free and esterified forms), including 10 di- and polyunsaturated acids, and the inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators, for 17 fatty acids (as methyl ester forms), were evaluated. Among the fatty acids tested, three n-3 polyunsaturated acids, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), exhibited potent inhibitory effects both on EBV-EA and NOR 1 activation. Furthermore, DHA methyl ester exhibited remarkable anti-tumor-promoting activity on an in vivo two-stage carcinogenesis test of mouse tumor using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
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PMID:Cancer chemopreventive effects of polyunsaturated fatty acids. 1503 55

A study of the chemical constituents of the stems of Derris trifoliata Lour. (Leguminosae) led to the isolation and identification of one new rotenoid, 6aalpha,12aalpha-12a-hydroxyelliptone ( 3), together with five other known rotenoids. In a search for novel cancer chemopreventive agents (anti-tumor promoters), we carried out a primary screening of five of the rotenoids isolated from the plant for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. The inhibitory activity of 3 was found to be equivalent to that of beta-carotene without any cytotoxicity. Deguelin ( 4) and alpha-toxicarol ( 5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that rotenoids might be valuable anti-tumor promoters.
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PMID:Cancer chemopreventive activity of rotenoids from Derris trifoliata. 1476 85

In order to identify antitumor-promoting agents, we performed primary in vitro screening of 31 coumarins isolated from 11 plants of the Citrus species (Rutaceae), examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of the 8-substituted coumarins, 8-formyl-7-hydroxycoumarin (5), osthenol (7), demethylauraptenol (8), osthenon (9) and dihydroosthenon (10), were found to significantly inhibit EBV-EA activation (IC50: 129-207 mol ratio/32 pmol TPA). Osthenol (7) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.
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PMID:Antitumor-promoting activity of coumarins from citrus plants. 1567 81

Three new chalcones, xanthoangelol I (1), xanthoangelol J (2), and deoxydihydroxanthoangelol H (3), were isolated from an ethyl acetate-soluble fraction of exudates of the stems of Angelica keiskei, and their structures were established on the basis of spectroscopic methods. Nine aromatic compounds of known structure, 4-12, and a diacetylene, 13, were also isolated and identified from this same fraction. On evaluation of these compounds for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, 1, 2, 4, and 9-12 showed potent inhibitory effects on EBV-EA induction. In addition, upon evaluation of the inhibitory effects against activation of (+/-)-(E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen oxide (NO) donor, six compounds, namely, 1, 2, 4, 9, 11, and 12, exhibited potent inhibitory effects. Further, isobavachalcone (4) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
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PMID:Chalcones and other compounds from the exudates of Angelica keiskei and their cancer chemopreventive effects. 1644 Oct 65

A series of lanostane-type triterpene acids, including eleven lucidenic acids (3, 4, 9, 10, 13-19) and six ganoderic acids (20-22, 24, 26, 27), as well as six sterols (28-33), all isolated from the fruiting bodies of the fungus Ganoderma lucidum, were examined for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, a known primary screening test for anti-tumor promoters. All of the compounds tested, except for ganolactone (27) and three sterols (29-31), showed potent inhibitory effects on EBV-EA induction, with IC(50) values of 235-370 mol ratio/32 pmol TPA. In addition, nine lucidenic acids (1, 2, 5-8, 11, 12, 18) and four ganoderic acids (20, 23-25) were found to inhibit TPA-induced inflammation (1 microg/ear) in mice, with ID(50) values of 0.07-0.39 mg per ear. Further, 20-hydroxylucidenic acid N (18) exhibited inhibitory effects on skin-tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter.
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PMID:Anti-inflammatory and anti-tumor-promoting effects of triterpene acids and sterols from the fungus Ganoderma lucidum. 1731 Dec 33

Several substituted cinnamylphenol (1,3-diphenylpropene) derivatives were synthesized and tested for their inhibitory activities against in vitro Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The prenylated cinnamylphenols were found to show remarkably potent activity. Furthermore, prenylated cinnamylphenols (19 and 25) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These results indicate that some prenylated cinnamylphenols might be valuable as potential cancer chemopreventive agents (anti-tumor promoters).
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PMID:Synthetic cinnamylphenol derivatives as cancer chemopreventive agents. 1731 10

The structures of six new lanostane-type triterpene acids isolated from the epidermis of the sclerotia of Poria cocos were established to be 15alpha-hydroxydehydrotumulosic acid (5), 16alpha,25-dihydroxydehydroeburicoic acid (9), 5alpha,8alpha-peroxydehydrotumulosic acid (10), 25-hydroxyporicoic acid H (11), 16-deoxyporicoic acid B (12), and poricoic acid CM (16) on the basis of spectroscopic methods. On evaluation of these six and 11 other known triterpene acids isolated from the sclerotium, 1-4, 6-8, 13-15, and 17, against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, all of the compounds except for 1, 3, 4, and 8 exhibited inhibitory effects with IC50 values of 195-340 mol ratio/32 pmol TPA. Compound 12 and poricoic acid C (13) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
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PMID:Triterpene acids from Poria cocos and their anti-tumor-promoting effects. 1748 30


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