12-Tetradecanoylphorbol 13-acetate

ALCOHOLS,HIGHERALIPHATIC - SURVEY AND NATURALALCOHOLSMANUFACTURE] (Voll) 12-O-Tetradecanoylphorbol 13-acetate... 

There are numerous reports of the effects of antioxidant vitamins on transformation. Vitamin C suppresses x-ray-induced transformation when CSHlOTy cells are treated daily for one week following irradiation (97), suppresses transformation by y-rays or neutrons, and prevents the promotion of radiation-induced transformation by 12-0-tetradecanoylphorbol 13-acetate (TPA), but has no effect on cell survival (98). In these studies, the continuous presence of vitamin C for a critical period appears to be necessary for suppression of transformation. Vitamin C may act on the promotion stage of... 

Many environmental toxins interact with specific cellular receptors, including enzymes, ion channels and ion pumps, and thus provide natural tools for the study of cellular signalling pathways. Palytoxin, a compound isolated from the coelen-terate of genus Palythoa, is one such useful and intriguing compound. The structure of palytoxin was first determined in 1981 independently by Hirata (7) and Moore (2). As one of the most potent marine toxins known, palytoxin has been studied in a variety of systems ranging from erythrocytes to neurons. As a tumor promoter of the non 12-O-tetradecanoylphorbol-13-acetate (TPA) type, palytoxin can also be studied in the context of a growth control system. 

KATiYAR s K and MUKHTAR H (1997) Inhibition of phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate-caused inflammatory responses in SENCAR mouse skin by black tea polyphenols . Carcinogenesis, 18 1911-16. 

In mouse models of skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), there is a close association between elevated XO activity in the epidermis and hyperplasia (Pence and Reiners, 1987). This association is also seen in psoriasis patients (Eisen and Seegmiller, 1961 Zimmer and Demis, 1966 Kizaki et al., 1977). In the study by Kizaki etal. (1977), the epidermis was increased about five-fold in comparison to normal. It is not known whether XO-derived ROS have any role in psoriatic epidermal hyperproliferation but low levels of hydrogen peroxide added to the culture medium are well known to induce skin fibroblast proliferation in vitro, an eflfect that is greatest at low passage numbers (Murrell et al., 1990). The generation of... 

Reiners, J.J. and Rupp, T. (1989). Conversion of xanthine dehydrogenase to xanthine oxidase occurs during keratinocyte differentiation modulation by 12-O-tetradecanoylphorbol-13-acetate. J. Invest. Dermatol. 93, 132—135. 

Reiners, J.J., Hale, M.A. and Cantu, A.R. (1988). Distribution of catalase and its modulation by 12-O-tetradecanoylphorbol-13-acetate in murine dermis and subpopulations of keratinocytes differing in their stages of differentiation. Carcinogenesis 9, 1259-1263. 

TPA-responsive element tyrosine receptor kinase A 12-0-tetradecanoylphorbol- 13-acetate sixth letter in the Hebrew alphabet zeta-associated protein 70... 

Cummins, C. L., Mangravite, L. M., Benet, L. Z., Characterizing the expression of CYP3A4 and efflux transporters (P-gp, MRP1, and MRP2) in CYP3A4-transfected Caco-2 cells after induction with sodium butyrate and the phorbol ester 12-0-tetradecanoylphorbol-13-acetate,... 

In animal studies, mirex, was tested at a dermal dose of 3.6 mg/kg 4 weeks in female CD-1 mice for tumor promoter activity and evidence of epidermal hyperplasia after initiation with 200 nmol/day 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. Positive control mice were treated with 2 nmol/day of the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), following initiation with DMBA. A third group of mice were treated with both 3.6 mg/kg mirex and 2... 

Meyer SA, Kim TW, Moser GL, et al. 1994. Synergistic interaction between the non-phorbol ester-type promoter mirex and 12-o-tetradecanoylphorbol-13-acetate in mouse skin tumor promotion. Carcinogenesis 15(1) 47-52. 

Fig. 6. Role of signal transduction pathways in phosphorylating H3 at Ser-10 and Ser-28. The Ras-MAPK (mitogen activated protein kinase) pathway is activated by EGF (epidermal growth factor) and TPA (12-0-tetradecanoylphorbol-13-acetate). UV-B activates both the Ras-MAPK pathway and the p38 kinase pathway (for more information about the signal transduction pathways see http // kinase, oci.utoronto.ca/signallingmap.html).

Phosphorylation of H3 is not limited to mitosis and also occurs in G1 phase of the cell cycle. Activation of the Ras-Raf-MEK-ERK signal transduction pathway and/or of the p38 stress kinase pathway when cells are treated with epidermal growth factor (EGF), 12-G-tetradecanoylphorbol-13-acetate (TPA), anesomycin, okadiac acid, and stresses such as UV irradiation induces the rapid phosphorylation of H3 at Ser-10 and/or Ser-28 [68-72] (Figs. 5 and 6). Inhibition of the MEK1,2 activity with PD98059 prevents the activation of ERK and TPA-induced H3... 

Long-chain ester derivatives of phorbol, a tetracyclic diterpene from the seed oil of Croton tiglium L., including its most abundant representative, 12-0-tetradecanoylphorbol-13-acetate (65), are potent activators of protein kinase G (PKG) and are used as standard tumor promoters for the study of experimental carcinogenesis in animal models." ... 

Dale IL, Bradshaw TD, Gescher A, Pettit GR (1989) Comparison of effects of bry-ostatins 1 and 2 and 12-0-tetradecanoylphorbol-13-acetate on protein kinase C activity in A549 human lung cardnoma cells. Cancer Res 49 3242-3245... 

McConkey DJ, Hartzell P, Jondal M, Orrenius S (1989) Inhibition of DNA fragmentation in thymocytes and isolated thymocyte nuclei by agents that simulate protein kinase C.) Biol Chem 264 13399-13402 McConkey DJ, Nicotera P, Orrenius S (1994) Signalling and chromatin fragmentation in thymocyte apoptosis. Immunol Rev 142 343-363 McCoy C, Smith DE, Cornwell MM (1995) 12-0-tetradecanoylphorbol-13-acetate activation of the MDRl promoter is mediated by EGRl. Mol Cell Biol 15 6100-6108... 

Wilson RE, Dooley TP, Hart IR (1989) Induction of tumorigenicity and lack of in vitro growth requirement for 12-0-tetradecanoylphorbol-13-acetate by transfection of murine melanocytes with v-Ha-ras. Cancer Res 49 711-716... 

In 2004, Fumkawa and co-workers reported the isolation of glybomine B (60) and glybomine C (61), along with glybomine A (42) (see Scheme 2.9), from the stem of G. arborea (68). This group of carbazole alkaloids showed antitumor-promoting activity against (12-0-tetradecanoylphorbol-13-acetate) TPA-induced EBV-EA activation. 

S. Sakurai, A. Ikeda, and M. Takido. Inhibitory effect of edible plant extracts on 12-o-tetradecanoylphorbol-13-acetate-induced ear oedema in mice. Phytother Res 1993 7(2) 185-189. 

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... 

Effect of CLA on Protein Kinase C (PKC) Activity. 12-0-tetradecanoylphorbol-13-acetate (TPA) administered by gavage induced the activity of ornithine decarboxylase (ODC) in a similar manner to that observed in mouse skin (28). The peak activity was about 5-times control and occurred 6 hrs after TPA intubation. Treating mice with CLA (100 mg p. o., twice per week) for 1, 2 or 4 weeks progressively reduced the TPA... 

RLV/Fischer rat assay without the addition of an exogenous metabolic activation system. In a single study, mouse JB6 epidermal cells were transformed by di(2-ethyl-hexyl) phthalate without activation and in one of two studies a weak response was reported in the CSHIOT A cell transformation assay with di(2-ethylhexyl) phthalate in either the absence or presence of exogenous metabolic activation. BALB/c-3T3 cells were not transformed by di(2-ethylhexyl) phthalate with or without metabolic activation. Di(2-ethylhexyl) phthalate inhibited gap-junctional intercellular communication in Chinese hamster V79 cells in six of seven studies, but not in one study of liver cells of cynomolgus monkeys in vivo. Di(2-ethylhexyl) phthalate treatment of Syrian hamster embryo cells in a two-stage exposure with 12-O-tetradecanoylphorbol 13-acetate resulted in superinduction of ornithine decarboxylase, an early event in morphological transformation no effect was seen after a one-stage treatment with di(2-ethylhexyl) phthalate alone. 

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