12-O-Tetradecanoylphorbol 13-acetate

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

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. 

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. 

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. 

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. 

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]. 

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. 

Oka, S., Yanagimoto, S., Ikeda, S., Gokoh, M., Kishimoto, S., Waku, K., Ishima, Y., and Sugiura, T. (2005). Evidence for the involvement of the cannabinoid CB2 receptor and its endogenous ligand 2-arachidonoylglycerol in 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation in mouse ear. J. Biol. Chem. 280, 18488—18497. 

Dermal exposure to benzene did not induce skin tumors in mice (Bull et al. 1986). No papillomas developed in mice that were given a 2-week, 800 mg/kg/day topical application of benzene as the initiator and a 1 pg topical application of 12-o-tetradecanoylphorbol-13-acetate 3 times a week for 20 weeks and observed for 52 weeks (Bull et al. 1986). The authors concluded that it is difficult to estimate benzene-induced tumor incidence after dermal exposure, and that mouse skin may not be the optimal study system. This is because of the high rate of false-negative responses to chemicals, like benzene, with recognized carcinogenic activity. 

NishlyamaT, SasakiT,Takalshi K, etal. (1994) rocp21 is involved In insulin-induced membrane ruffling and rho p21 is involved in hepatocyte growth factor- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced membrane ruffling in KB cells. In Mol. Cell. Biol. 14 2447-2456. 

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]. 

Polyporenic acids A and C have anti-inflammatory activity and, in a bioassay for potential anti-tumour activity, suppressed the oedema induced by 12-O-tetradecanoylphorbol-13-acetate. 

The studies were carried out on a primary screening test using their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol- 13-acetate (TPA), a strong promoter, in Raji cells. 

---