TPA induced skin tumors

Skin 1 Inhibition of 7,12-dimethylbenz[a Janthracene (DMBA 2)/TPA induced skin tumors (Topical application) [8,3739-42]... 

Skin 11 Inhibition of DMBA/TPA induced skin tumors (Oral application) [43]... 

Assay for Iinhibition of DMBA/TPA Induced Skin Tumors in Mice... 

Huang et al. [70] have evaluated the effects of chlorogenic acids on tumor promotion in an animal study using CD-I mice. Chlorogenic, caffeic and ferulic acids inhibit the induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA-mediated DNA synthesis has been weakly inhibited, but TPA-induced skin tumor promotion has been markedly inhibited by these compounds. 

Inhibition of A -nitrobis-(2-hydroxypropyl)amine (BHP) induced pancreatic tumors Inhibition of DMBA/TPA induced skin tumors Inhibition of DMBA/teleocidin B induced skin tumors Inhibition of DMBA/fumonsin-Bl induced skin tumors Inhibition ofNOR-l/TPA induced skin tumors Inhibition of DMBA/okadaic acid induced skin tumors Inhibition of DMBA/mineral oil induced skin tumors... 

Gingerol, a prineipal pungent ingredient of ginger, strongly inhibited TPA-induced skin tumor promotion when topieally applied onto dorsal skin of female ICR mice... 

The Protective Effect of DBM on TPA-induced Skin Tumor Promotion in CD-I Mice Previously Initiated with DMBA... 

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... 

For the highly inhibitive compounds in the TPA-induced inflammatory assay, we evaluated their antitumor-promoting activity by a standard initiation-promotion protocol [Fig. (3)] [37,40]. Initiation was achieved by a single application of 50 pg of DMBA (2), a well known tumor initiator, to the skin of backs of 8-week-old female ICR mice. From one week after initiation, 1 pg of TPA (1) was applied twice a week until week 20. The test compound (2.0 or 0.2 pM) dissolved in acetone-dimethyl sulfoxide (DMSO) (9 1, 100 pi) was applied 30 min before each TPA treatment. Groups of 15 mice were used. The number of tumors was counted weekly. 

Induction of epidermal ODC is a characteristic biochemical alteration elicited by TPA and may be representative of the effects of phorbol esters with strong tumor promoting activity [81]. A single application of TPA (5 pg) resulted in a substantial and transient increase of epidermal ODC activity in mice with a peak at about 4 h after TPA treatment, and the induction was potently inhibited by treatment (5 pM) of the mouse skin with sitosterol (33, 65% inhibition) and three lupane type triterpenoids betulin (255 79%), betulinic acid (257 89%), and lupeol (264,96%) [30]. The inhibitory effect on TPA-induced ODC activity was further reported for ursolic acid (210 45% inhibition at 2.0 pM/5nM of TPA) [31]. 

Soyasapogenol B, soyasaponins I and II and wistariasaponins from Wistaria brachybotrys (wistariasaponin C corresponds to astragaloside VIII) decreased (20-30%) the Epstein-Barr Virus (EBV) activation induced by the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate) in Raji cells at a concentration of lxlO2 mol ratio [151]. Soyasaponin I from the same plant exhibited remarkable inhibitory effects on mouse skin tumor promotion on the basis of the two-stage DMBA-TPA carcinogenesis test in vivo. Soyasaponin I reduced the number of papillomas per mouse at about 40% even at 20 weeks [152]. 

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