Tetradecanoylphorbol-13-acetate model

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... 

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." ... 

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],... 

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]. 

Among the models of inflammation in vivo, those that involve the skin have the particular advantage that the results are immediately and continuously observable. Models of skin inflammation are numerous and varied, ranging from acute and limited to chronic and tissue-destructive. Croton oil, different phorbol esters, principally 12-tetradecanoylphorbol-13-acetate (TPA), AA and oxazolone, provide a range of skin inflammation models suitable for the evaluation of both topical and/or... 

Palytoxin was identified as a skin tnmor two decades ago. Palytoxin is a potent tumor promoter in the monse skin carcinogenesis model. The biochemical mechanism of action of palytoxin as a tnmor promoter differs significantly from that of the prototypical phorbol ester tumor promoters. In contrast to the skin tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA), palytoxin does not activate protein kinase C or increase ornithine decarboxilase activity in the mouse skin. " There are several interesting stndies on the cellnlar mechanisms activated by palytoxin as a tumor promoter however, the biochemical mechanisms by which palytoxin-stimnlated signaling contribntes to tnmor promotion are cnrrently elncidated, and it seems that they conld depend on the experimental... 

INK. Antioxidants can attenuate MAPK activation, suggesting that the MAP kinase cascade, including activation of NF-kB and AP-1, is affected by ROS levels in cells. ° Activation of MAP kinases may to play a role in the pathogenesis of cancer. Application of 12-0-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, which acts through a fiee-radical-mediated mechanism, to the ears and dorsal skin of mice induced a rapid and sustained activation of ERKl/2 and p38 MAP kinase. NF-kB activation in this model was abolished by the ERKl/2 inhibitor U0126, while SB203580, a p38 inhibitor, had no effect. In human hepatoma cells, ROS-induced in cell proliferation correlated well with ERK activation, but not INK or p38. Pathways recently, p38 MAP kinase has been shown to coprecipitate with p53 and phosphoiylates p 3 93,94 p33 observed to phosphoiylate p53 when exposed to DNA-damaging... 

Resveratrol has been reported to inhibit all three stages of carcinogenesis initiation, progression, and promotion in several types of cancer. Several reports suggested that resveratrol inhibits cancer initiation in various model systems. Sharma et al. found that resveratrol reduced 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced free-radical formation in human promyelocytic leukemia cells HL-60. In another model, resveratrol also inhibited 7,12-dimethylbenzfi3)anthracene (DMBA)-induced preneoplastic lesion in... 

Procyanidin B2 (dimer), isolated from loquat leaves, was found to inhibit the 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced activation of Epstein-Barr virus early antigen in Raji cells [108]. Animal studies and cell models suggest that flavonoids act as anticarcinogens through influencing molecular events in the initiation, promotion, and progression stages of cancer [109]. 

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