Polymeric black tea polyphenols modulate the localization and activity of 12-O-tetradecanoylphorbol-13-acetate-mediated kinases in mouse skin: mechanisms of their anti-tumor-promoting action
| Autor: | Prerana Dange, Asha G. Ramchandani, Vaishali Kailaje, Gaurav Kumar, Girish B. Maru, Milind M. Vaidya |
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| Rok vydání: | 2012 |
| Předmět: |
Curcumin
Administration Topical Protein Serine-Threonine Kinases 12-O-Tetradecanoylphorbol-13-acetate Biochemistry Camellia sinensis Cell Line chemistry.chemical_compound Mice Phosphatidylinositol 3-Kinases Physiology (medical) polycyclic compounds Animals Anticarcinogenic Agents Humans Protein Isoforms Phosphatidylinositol Phosphorylation Protein Kinase Inhibitors Protein kinase C Protein Kinase C Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Skin integumentary system Chemistry Kinase Plant Extracts Polyphenols Pyruvate Dehydrogenase Acetyl-Transferring Kinase Molecular biology Plant Leaves Cytosol Protein Transport Carcinogens bacteria Tetradecanoylphorbol Acetate Tumor promotion Female Signal transduction Apoptosis Regulatory Proteins Proto-Oncogene Proteins c-akt |
| Zdroj: | Free radical biologymedicine. 53(6) |
| ISSN: | 1873-4596 |
| Popis: | Polymeric black tea polyphenols (PBPs) have been shown to possess anti-tumor-promoting effects in two-stage skin carcinogenesis. However, their mechanisms of action are not fully elucidated. In this study, mechanisms of PBP-mediated antipromoting effects were investigated in a mouse model employing the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Compared to controls, a single topical application of TPA to mouse skin increased the translocation of protein kinase C (PKC) from cytosol to membrane. Pretreatment with PBPs 1–3 decreased TPA-induced translocation of PKC isozymes (α, β, η, γ, e) from cytosol to membrane, whereas PBPs 4 and 5 were less effective. The levels of PKCs δ and ζ in cytosol/membrane were similar in all the treatment groups. Complementary confocal microscopic evaluation showed a decrease in TPA-induced PKCα fluorescence in PBP-3-pretreated membranes, whereas pretreatment with PBP-5 did not show a similar decrease. Based on the experiments with specific enzyme inhibitors and phosphospecific antibodies, both PBP-3 and PBP-5 were observed to decrease TPA-induced level and/or activity of phosphatidylinositol 3-kinase (PI3K) and AKT1 (pS473). An additional ability of PBP-3 to inhibit site-specific phosphorylation of PKCα at all three positions responsible for its activation [PKCα (pT497), PKC PAN (βII pS660), PKCα/βII (pT638/641)] and AKT1 at the Thr308 position, along with a decrease in TPA-induced PDK1 protein level, correlated with the inhibition of translocation of PKC, which may impart relatively stronger chemoprotective activity to PBP-3 than to PBP-5. Altogether, PBP-mediated decrease in TPA-induced PKC phosphorylation correlated well with decreased TPA-induced NF-κB phosphorylation and downstream target proteins associated with proliferation, apoptosis, and inflammation in mouse skin. Results suggest that the antipromoting effects of PBPs are due to modulation of TPA-induced PI3K-mediated signal transduction. |
| Databáze: | OpenAIRE |
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