12-0-Tetradecanoyl-phorbol-13-acetate

Whelan RD, Kiley SC, Parker PJ (1999) Tetradecanoyl phorbol acetate-induced microtubule reorganization is required for sustained mitogen-activated protein kinase activation and morphological differentiation of U937 cells. Cell Growth Diff 10 271-277... 

Tumor necrosis factor inhibition. Ethanol (95%) extract of the rhizome, in cell culture at a concentration of 100 pg/mL, was inactive on macrophage cell line RAW 264.7 vs EPS induction of TNF-az° zp Tumor promotion inhibition. Ethyl acetate and methanol extracts of the dried rhizome, in cell culture at a concentration of 50 pg/mL, produced weak activity on G3H/ lOTl/2 cells vs tetradecanoyl phorbol acetate-induced acetate phospholipid synthesis. The hexane extract was inactiveZ . Ethanol (95%) and petroleum ether extracts of the dried rhizome, in cell culture at a concentration of 160 and 80 pg/mL, re-... 

A property of the protein kinase C enzyme family that is highly valuable for their identification and characterization is their activation by tumor promoters such as phorbol esters (Fig. 7.7). Protein kinase C binds to the tumor promoter, tetradecanoyl phorbol acetate (TPA), with high affinity and is activated by this binding. The specific activation of protein kinase C by phorbol esters is an important tool to demonstrate their involvement in signal transduction pathways. By external addition of TPA, it is possible to use cellular model systems to test which biological responses of a signal transduction pathway involve, and are controlled by, protein kinase C. 

Fig. 7.7. Structure of tetradecanoyl phorbol acetate (TPA). Tetradecanoyl phorbol acetate functions as a tumor promoter and is a specific activator of protein kinase C.

Anthracene. Anthracene has been found to be inactive as an initiating agent under a dermal initiation/promotion protocol using tetradecanoyl phorbol acetate (TPA) as the promoter (LaVoie et al. 1983a). 

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. 

Schlatterer K, Krauter G, Schlatterer B, Hecker E, Chandra P (1999) A novel protein (plO) induced by 12-0-tetradecanoyl-phorbol-13-acetate (TPA) and other hy-perplasiogenic tumor-promoting and non-promoting agents in murine epidermis. Anticancer Res 19 397-404... 

Craciani, V, Mikalsen, S.-O., Vasseur, P. Sarmer, T. (1997) Effects of peroxisome proliferators and 12-0-tetradecanoyl phorbol-13-acetate on intercellular communication and cotmexin43 in two hamster fibroblast systems. Int. J. Cancer, 73, 240-248 Curto, K.A. Thomas, J.A. (1982) Comparative effects of diethylhexyl phthlate or mono-ethylhexyl phthlate on male mouse and rat reproductive organs. Toxicol, appl. Pharmacol., 62, 121-125... 

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. 

Dichloroacetonitrile was tested in a limited carcinogenicity study in female SEN mice by skin application, in an initiation/promotion study in female SEN mice by skin application and in a screening assay for lung tumours in female strain A mice by oral administration. No skin tumour was produced after skin application in mice or in the initiation/promotion study, in which dichloroacetonitrile was applied topically as six equal doses over a two-week period, followed by repeated doses of 12-0-tetradecanoyl-phorbol 13-acetate for 20 weeks. There was no increase in either the proportion of mice with lung tumours or the number of lung tumours per mouse (lARC, 1991). 

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. 

Figure 1. General structure of the tumor-promoting component, phorbol, of croton oil. 12-O-tetradecanoyl-phorbol-l3-acetate (TPA) is the most potent promoter of the phorbol diesters. Phorbol didecanoate and phorbol dibenzoate, among others, have promoting ability but to a lesser extent than TPA. Phorbol alone has been reported to have no capacity to induce tumors as ODC.

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). 

Mass spectral fragmentation of the products of electron-impact fragmentation of 6-nitro-2,l-benzisoxazole (6-nitroanthranil) [1351], 3-substituted 6-nitroanthranils [1352], 4-arylamino-5,7-dinitrobenzofurazan [747], 4-(2-aminoethylamino)-7-ni-trobenzofurazan [1353], 12-O-tetradecanoyl phorbol-13-O-acetate containing 4-nitrobenzofurazan [1354], and fluorescent probes on the base nitrobenzofurazans [777] have been discussed. 

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