12-0-Tetradecanoylphorbol 13-acetate inhibition

Both bryostatin 1 and 12-0-tetradecanoylphor-bol-13-acetate inhibited lymphocyte antibody-dependent cell-mediated cytotoxicity such that, at a 20 1 effector-to-target ratio, control lymphocytes had a mean 49 12% specific Cr release of antibody-coated target cells while bryostatin 1 and 12-O-tetradecanoylphorbol-13-acetate cultured lymphocytes had 12 6 and 8 12%, respectively, in four experiments (Tilden and Kraft 1991). 

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. 

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... 

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... 

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... 

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. 

Murakoshi, M., Nishino, H., Tokuda, H., Iwashima, A., Okuzumi, J., Kitano, H., and Iwasaki, R. (1992). Inhibition by squalene of the tumor promoting activity of 12 o-tetradecanoylphorbol-13 acetate in mouse skin carcinogenesis. Int. ]. Cancer 52,950-952. 

Sarcophytols A (46) and B (47) are simple cembranoids isolated from the Okinawan soft coral S. glaucum and have been reported to possess potent inhibitory activities against various classes of tumor promoters.70 71 Sarcophytol A (46) mediated dose-dependent diminution of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced transformation of JB6 cells.72 When evaluated for potential to inhibit TPA-induced JB6 cell transformation, several of the sarcophine metabolites (48 to 58) mediated inhibitory responses greater than sarcophytol A (46) or sarcophine (45), most notably 7a-hydroxy-y8(19) deepoxysarcophine (50), which was comparable to 13-cz s-retinoic acid. These studies provide a basis for further development of novel furanocembranoids as anticancer agents. 

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. 

Assays for the inhibition of croton oil-induced edema, teleosidin-induced edema, and 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced edema in animals are used as rapid in vivo preliminary tests for screening antitumor-promoting substances [1],... 

In the classic model of initiation and promotion, conventional tumor promoters (CTP) inhibit the intracellular mechanisms that can eliminate the nascent clone, facilitate accumulation of the mutations necessary for full malignant transformation, or disrupt intercellular signaling [15], A classic example of a CTP is 12-O-tetradecanoylphorbol- l 3-acetate (TPA, also referred to as phorbol myristate acetate, PMA). The mechanisms proposed for CTP that are relevant for the tumor types associated with immunosuppression, such as nonmelanoma skin tumors and lymphomas, are listed in Table 27.3. The table is limited to mechanisms of promotion and does not include tumor initiation mechanisms, namely those that directly or indirectly damage DNA (e.g., free radicals mediated by metabolism of ethanol) [16] or are mechanisms of neovasularization (e.g., angiogenesis in response to UV-A and B) [17], The table also excludes mechanisms of CTP that have only been studied in the context of irrelevant tumors, such as TCDD in hepatocarcinogenesis [18],... 

Katiyar, S.K. et al.. Inhibition of 12-0-tetradecanoylphorbol-13-acetate and other skin tumor-promoter-caused induction of epidermal interleukin-1 alpha ruRNA and protein expression in SENCAR mice by green tea polyphenols, J. Investig. Dermatol., 105, 394, 1995. 

Application of rosemary to mouse skin inhibited covalent binding of benzo(a)pyrene to epidermal DNA and inhibited tumor initiation by benzo(a)pyrene [B(a)P] and 7,12-dimethylbenz(a)anthracene (DMBA). Topical application of 1, 3 or 10 pmol camosol together with 5 nmol 12-0-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63 and 78%, respectively. 

Forty-eight derivatives of berberine-type alkaloids were examined for their inhibition activity against the induction of mouse ear edema via application of 12-O-tetradecanoylphorbol-13-acetate (TPA). Berberrubine chloride displayed inhibitory effects (ED50 1.3 pmol/ear 52% inhibition). Berberine derivatives had stronger inhibitory activity than palmatine derivatives. Since berberine and some of its derivatives are present in Chinese traditional drugs, which are used in combined Kampo prescriptions, it is important to determine if such alkaloids possess carcinogenic inhibiting properties [221]. 

Isotetrandrine was found to inhibit arachidonic acid-induced inflammation in mice. Topical application of isotetrandrine (2 pmol/mouse) markedly suppressed the tumor-promoting effect of 12-O-tetradecanoylphorbol-13-acetate (1 pg) in mouse skin initiated with 7,12-dimethylbenz[a]anthracene (50 pg), at a grade corresponding to that of another bisbenzylisoquinoline alkaloid, cepharanthine [197]. 

Ethanolic extract (50%) of M. oleifera (whole plant excluding roots) shows anti-cancer activity in mice (50). Evaluation of the anticancer potential of 11 plants used in Bangladeshi folk medicine has shown that, only three extracts, among which M oleifera, is considered as a potential source of anticancer compounds (56). Crude ethanol extract of M. oleifera dried seeds inhibits the formation of Epstein-Barr virus-early antigen (EBV-EA) induced by 12-0-tetradecanoylphorbol-13-acetate. At a dosage of 100 pg/mL, the extract inhibits EBV-EA formation by 100% suggesting its antitumor-promoting activity (99). 

Another fungus, Poria cocos, which is also used in Chinese traditional medicine, contains a range of hydroxylated lanostanes, including the poricoic acids, e.g. poricoic acid A (5.167), which inhibit the tumour promoting elfects of 12-0-tetradecanoylphorbol-13-acetate and possess cytotoxic elfects against human cancer cell lines. 

Carragenin-induced paw edema and 12-0-tetradecanoylphorbol 13-acetate (TPA)-induced edema have been used as experimental models of acute inflammation. Gomisin A (49), gomisin J (140), and wuweizisu C (141) inhibited inflammation induced by TPA in mice [44], Diphyllin acetyl apioside (142) and diphyllin apioside (tuberculatin) (143) also showed an anti-inflammatory effect with IDjg values of 0.27 and 1.23 pM/ ear, respectively, in rabbit [98]. 

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