12-O-tetradecanoyl-phorbol-13-acetate

Recent studies have demonstrated that lithium (and to a lesser extent VPA) produces, at therapeutically relevant concentrations, complex alterations in basal and/or stimulated DNA-binding of 12-o-tetradecanoyl-phorbol 13-acetate (TPA) response element (TRE) to AP-1 transcription factors. These alterations are produced not only in human SH-SY5Y cells in vitro, but also in rodent brain following chronic, in vivo administration [5, 7, 15-21]. Corresponding to an increase in basal AP-1 DNA-binding activity, lithium and VPA have been shown to increase the expression of a luciferase reporter gene driven by an SV40 promoter that contains TREs in a time- and concentration-dependent fashion. Mutations in the TRE... 

R. Mentlein, The Tumor Promoter 12-O-Tetradecanoyl Phorbol 13-Acetate and Regulatory Diacylglycerols are Substrates for the Same Carboxylesterase , J. Biol. Chem. 1986, 261, 7816-7818. 

Yancey SB, Edens JE, Trosko JE, Chang C, Revel JP Decreased incidence of gap junctions between Chinese hamster V-79 cells upon exposure to the tumor promotor 12-O-tetradecanoyl phorbol-13-acetate. Exp Cell Res 1982 139 329-340. 

Several effects of forskolin on B-lymphocytes, the cells of the immune system responsible for the production of immunoglobulins, have further been reported. This diterpene was found to inhibit cellular proliferation of B cells stimulated either by antibodies to surface immunoglobulins (anti-mu), and an antibody to CD20 antigen or 12-O-tetradecanoyl phorbol 13-acetate [219]. There was also a clear inhibition of G1 entry and DNA synthesis, and forskolin maintained its inhibitory effect even when added later after anti-mu stimulation. Additionally, no differences were found in the inhibitory effect of forskolin on neoplastic B cells, as compared to the responses of normal cells. Growth inhibition associated with an accumulation of cells in G1 was later found when cells of the B-lymphoid precursor cell line Reh were incubated with forskolin [220]. In that study, a delay of cells in G2/M prior to G1 arrest was observed, suggesting that important restriction points located in the G1 and G2 phases of the cell cycle may be controlled by forskolin (due to cAMP levels elevation). In a subsequent study [221], it was found that the arrest of Reh cells was accompanied by rapid dephosphorylation of retinoblastoma protein, which was suggested to be a prerequisite for the forskolin mediated arrest of these cells in Gl. 

Note FAP familial adenomatous polyposis ACF aberrant crypt foci FAD focal areas of dysplasia B[a]P benzo[a]pyrene DMBA 7,I2-dimethylbenz[a]nthracene TPA 12-O-tetradecanoyl-phorbol-13-acetate NNK 4-(methyl-nitrosamino)-I-(3-pyridyl)-l-butanone NQO 4-mtroquinoline 1-oxidase DMAB 3,2 -dimethyl-4-aminobiphenol PhIP 2-amino-l-methylimidazo[4,5-b]pyridine DHPN 2,2 -dihydroxy-di-n-propylnitrosamine EHEN jV-ethyl-jV-hydroxyethylnitrosamine. 

Meier, B Radeke, H.H., Selle, S., Habermehl, G.G., Resch, K Sies, H. (1990). Human fibroblasts release low amounts of reactive oxygen species in response to potent phagocyte stimulants, N-formylmethionylleucylphenylalenine, leukotriene B4 or 12-O-tetradecanoyl phorbol-13-acetate. Biol. Chem. Hoppe Seyler 371,1021-1025. 

Aniseed possesses anti-inflammatory properties. Topical application of ethyl acetate and hexane extracts of aniseed, at a dose of 20 pi/ animal, produced an anti-inflammatory effect in mouse treated with 12-O-tetradecanoyl phorbol-13-acetate (Okuyama eta/., 1995). 

Nishino, H. Okuyama, T. Takata, M. Shibata, S. Tokuda, H. Takayasu, J. Hasegawa, T. Nishino, A. Ueyama, H. Iwashima, A. Studies on the anti-tumor-promoting activity of naturally occurring substances IV. Pd-H [(+)anomalin, (- -)praeruptorin B], a seselin-type coumarin, inhibits the promotion of skin tumor formation by 12-O-tetradecanoyl-phorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated mice. Carcinogenesis (London), 1990, 11 1557-1561. 

Azuine MA, Tokuda H, Takayasu J, et al. (2004) Cancer chemopreventive effect of phenothiazines and related tri-heterocyclic analogues in the 12-O-tetradecanoyl-phorbol-13-acetate promoted Epstein-Barr virus early antigen activation and the mouse skin two-stage carcinogenesis models. Pharmacology Research 49 161-169. 

Sasaki K, Mizusawa H, Ishidate M (1988) Isolation and characterization ofras-transfected BALB/3T3 clone showing morphological transformation by 12-O-tetradecanoyl-phorbol-13-acetate. Jpn J Cancer Res 79 921-930... 

Abies sachalinensis (C.F.Schmidt) Mast, (bark) Spirobiflavonoids (abiesinols). All compounds exhibited potent inhibitory effects on ( )-(iI)-methyl-2-[( )-hydroxyimino]-5-nitro-6-methoxyhex-3-enamide (NOR 1) activation. A spirobiflavonoid showed remarkable anti-tumor-initiating activity in the in vivo two-stage mouse skin carcinogenesis test using peroxynitrite (ONOO PN) as the initiator and 12-O-tetradecanoyl-phorbol- 13-acetate (TPA) as the promoter. Wada et al., 2010[476]. 

Miyake A, Yamamoto H, Kubota E, Hamaguchi K, Kouda A, Honda K, Kawashima H. Suppression of inflammatory responses to 12-O-tetradecanoyl-phorbol-13-acetate and carrageenin by YM-26734, a selective inhibitor of extracellular group II phospholipase A2. Br J Pharmacol 1993 110 447-453. 

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