EBV-EA activation induced by TPA

EBV Inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA [22-27]... 

Several terpenoids have been evaluated for their inhibitory effects on EBV-EA activation induced by TPA. Table 6 shows the inhibitory effects of monoterpenoids [70,71], sesquiterpenoids [20,119-123], diterpenoids [21,123-131], and meroterpenoids [117] against TPA (32 pmol, 20 ng)-induced EBV-EA activation in Raji cells. The inhibitory effects were compared with that of [3-carotene, a vitamin A precursor that has been studied intensively in cancer chemoprevention using animal models [2,4]. All of the terpenoids tested caused higher viability (60-80%) of Raji cells even at mol ratio of compound to TPA = 1000 1 indicating their very low cytotoxicity at that high concentration (refer to Table 6). 

Many kinds of steroids and their glycosides were tested for their inhibitory effects on EBV-EA activation induced by TPA [63]. Of these steroids, though cardiac steroids and their glycosides had strong cytotoxicities against Raji cells at 1 x 10 mol ratio/TPA, they exhibited stronger inhibitory effects at lower concentration than other steroids. 

The studies were carried out on a primary screening test using their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol- 13-acetate (TPA), a strong promoter, in Raji cells. 

Glycyrrhetic acid (147) and retinoic acid are known in vivo antitumor-promoters which inhibit EBV-EA induction by tumor promoters [77]. Oleanolic acid (142) and ursolic acid (210) significantly inhibit the activation induced by TPA and teleocidin B (3) as do 147 and retinoic acid... 

On the basis of the results of the in vitro assays (inhibitory effects on EBV-EA activation and effects on the cell cycle of Raji cells induced by the promoter, TPA), the anti-tumor-promoting activities of 59 and 66 on the two-stage carcinogenesis test would be expected. 

Epstein-Barr virus early antigen induction. Methanol extract of the dried leaf, in cell culture at a concentration of 1 pg/mL, was inactive. The assay was designed for tumor-promoting activity . Two diastere-oisomers of 2,7,1 l-cembratriene-4,6-diol (a- and 3-CBT) from the neutral fractions of cigarette smoke condensate, in Raji cells, produced potent inhibitory effects on the induction of Epstein-Barr virus (EBV)-EA by 12-0-tetradecanoylphorbol-13-acetate (TPA). The doses of a- and P-CBT required for 50% inhibition of EBV-EA induction by TPA were 7.7 and 6.7 mg/mL, respectively. Application of a- and P-CBT to mouse skin before treatment with TPA, inhibited TPA-induced ornithine decarboxylase activity in a dose-dependent manner. Application of 16.5 pM/mouse of a- and p-CBT resulted... 

A test of inhibitory effects on Epstein-Barr virus early antigen activation in Raji cells induced by a combination of n-butylic acid and 12-0-tetradecanoylphorbol-13-acetate (TPA) has been employed (EBV-EA test) as a simple primary screening for antitumor promoting agents. In this test, significant inhibitory effect was observed for astilbin and its isomers as well as (+)-taxifolin. Of these dihydroflavonol derivatives, neoastilbin showed the strongest activity. 

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