• Title/Summary/Keyword: phorbol ester

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CELECOXIB INHIBITS PHORBOL ESTER-INDUCED PGE$_2$ PRODUCTION AND COX-2 EXPRESSION BY TARGETING OF p38 MAP KINASE AND AP-1 IN MOUSE SKIN

  • Chun, Kyung-Soo;Surh, Young-Joon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.175-175
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    • 2002
  • Celecoxib, a selective COX-2 inhibitor, has been reported to prevent experimentally induced colon, breast, bladder, and skin carcinogenesis. Moreover, daily intake of celecoxib resulted in significant reduction of polyps in patients with familial adenomatous polyposis.(omitted)

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Curcumin Inhibits Phorbol Ester-induced Expression of Cyclooxygenase-2 in Mouse Skin through Suppression of Extracellular Signal-Regulated Protein Kinase Activity and NF-$\kappa$B Activation

  • Chun, Kyung-Soo;Surh, Young-Joon
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.147.3-148
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    • 2003
  • Recently, there have been considerable efforts to search for naturally occurring substances for the intervention of carcinogenesis. Curcumin, a yellow coloring ingredient of turmeric (Curcuma longa L., Zingiberaceae), has been shown to inhibit experimental carcinogenesis and mutagenesis, but molecular mechanisms underlying its chemopreventive activities remain unclear. In the present work, we found that curcumin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of CPX-2 in female ICR mouse skin when applied topically 30 min prior to TPA as determined by both immunoblot and immunohistochemical analyses. (omitted)

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Inhibitory effects of [6]-gingerol on phorbol ester-induced cox-2 expression in mouse skin: p38 mapk and p65/rela as possible molecular targets

  • Kim, Sue-Oko;Chun, Kyung-Soo;Surh, Young-Joon
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.149.3-150
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    • 2003
  • [6]-Gingerol, a major pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying anti-tumor promoting effects of [6]-gingerol on mouse skin carcinogenesis. (omitted)

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Chlorination of ortho-position on Polychlorinated Biphenyls Increases Protein Kinase C Activity in Neuronal Cells

  • Lee, Youn-Ju;Yang, Jae-Ho
    • Toxicological Research
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    • v.28 no.2
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    • pp.107-112
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    • 2012
  • Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental pollutants. Recently, it is suggested that neurotoxic effects such as motor dysfunction and impairment in memory and learning have been associated with PCB exposure. However, structure relationship of PCB congeners with neurotoxic effects remains unknown. Since PKC signaling pathway is implicated in the modulation of motor behavior as well as learning and memory and the role of PKC are subspecies-specific, we attempted to study the effects of structurally distinct PCBs on the total PKC activity as well as subspecies of PKC in cerebellar granule cell culture model. Cells were exposed to 0, 25 and 50 ${\mu}M$ of PCB-126, PCB-169, PCB-114, PCB-157, PCB-52 and PCB-4 for 15 min. Cells were subsequently analyzed by [$^3H$] phorbol ester binding assay or immunoblotted against PKC-${\alpha}$ and -${\varepsilon}$ monoclonal antibodies. While non-dioxin-like-PCB (PCB-52 and PCB-4) induced a translocation of PKC-${\alpha}$ and -${\varepsilon}$ from cytosol to membrane fraction, dioxin-like PCBs (PCB-126, -169, -114, -157) had no effects. [$^3H$] Phorbol ester binding assay also revealed structure-dependent increase similar to translocation of PKC isozymes. While PCB-4 induced translocation of PKC-${\alpha}$ and -${\varepsilon}$ was inhibited by ROS inhibitor, the pattern of translocation was not affected in presence of AhR inhibitor. It is suggested that PCB-4-induced PKC activity may not be mediated via AhR-dependent pathway. Taken together, our findings suggest that chlorination of ortho-position in PCB may be a critical structural moiety associated with neurotoxic effects, which may be preferentially mediated via non-AhR-dependent pathway. Therefore, the present study may contribute to understanding the neurotoxic mechanism of PCBs as well as providing a basis for establishing a better neurotoxic assessment.

Studies on the activity of telomerase in the mouse skin carcinogenesis (마우스피부암 발생과정에 있어서 텔로머레이저 활성에 관한 연구)

  • Kang, Ho-Il;Jee, Sung-Wan;Kim, Ok-Hee
    • Environmental Mutagens and Carcinogens
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    • v.25 no.2
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    • pp.66-70
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    • 2005
  • Telomerase, a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes, has activity in most malignant tumors and provides a mechanism for the unlimited potential for division of neoplastic cells. Although telomerase is known to be a regulated enzyme, the factors and mechanisms involved in telomerase regulation are not well understood. In the present study, we compared the effect of 12-O­tetradecanoyl-phorbol-13-acetate (TPA) and non-phorbol ester tumor promoters such as okadaic acid, anthralin and benzoyl peroxide on the expression of telomerase in the mouse skin carcinogenesis system, a well characterized model for studying pre-malignant and malignant progression. We found that most early papillomas harvested after 10 weeks of TPA promotion showed telomerase activity. Other papillomas harvested after 10 weeks of okadaic acid, anthralin and benzoyl peroxide promotion and after single treatment of DMBA only also showed telomerase activity, respectively. On the other hand, normal and all skins surrounded by papillomas harvested after 10 weeks of these promoters has no telomerase activity. Taken together these results, there appears to be no clear association between the level of telomerase activity and protein phosphorylation in mouse skin papillomas and telomerase may be useful as bio-markers in early detection of tumors.

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Effects of Curcumin and Genistein on Phorbol Ester or Tumor Necrosis Factor-${\alpha}$-Induced Mucin Production from Human Airway Epithelial Cells

  • Lee, Su-Yel;Lee, Hyun-Jae;Lee, Jae-Woo;Jeon, Byeong-Kyou;Kim, Ju-Ock;Lee, Choong-Jae
    • Tuberculosis and Respiratory Diseases
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    • v.70 no.3
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    • pp.218-223
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    • 2011
  • Background: We investigated whether curcumin and genistein affect the MUC5AC mucin production from human airway epithelial cells that is induced by phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). Methods: Confluent NCI-H292 cells were pretreated with each agent for 30 min and then stimulated with PMA or TNF-${\alpha}$ for 24 hours. MUC5AC mucin production was measured by an ELISA. Results: (1) Curcumin dose-dependently inhibited the production of MUC5AC mucin that was induced by PMA or TNF-${\alpha}$; (2) Genistein inhibited PMA-induced MUC5AC mucin production. However, it did not decrease TNF-${\alpha}$-induced MUC5AC mucin production. Conclusion: These results suggest that curcumin and genistein inhibit the production of airway mucin induced by PMA.

Design and Synthesis of Bioisosteres of Ultrapotent Protein Kinase C(PKC) Ligand, 5-Acetoxymethyl-5-hydroxymethyl-3-alkylidene tetrahydro-2-furanone

  • Lee, Jee-Woo
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.452-457
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    • 1998
  • Three compounds, 5-(acetoxymethyl)-5-(hydroxymethyl)-3-tetradecyl-2,5-dihydro-2-furanone (3), 5-(acetoxymethyl)-5-(hydroxymethyl)-3,3-dihexyltetrahydro-2-furanone (4) and 5-(acetoxymethyl)-5-(hydroxymethyl)-3,3-dioctyltetrahydro-2-furanone (5), were designed and synthesized as surrogates of the ultrapotent DAG analogue, 5-(acetoxymethyl)-5-(hydroxymethyl) 3-[(Z)-tetradecylideneltetrahydro-2-furanone (1), a compound that showed high affinity for PKC-$\alpha$ ($K_1$=35 nM) in a competition binding assay with [$^3H$-20]phorbol-12,13-dibutyrate (PDBU). In an attempt to overcome the problem of generating geometrical E- and Z- isomers, as encountered with 1, the double bond was moved to an endocyclic location as in 3, or an additional alkyl chain was appended to C3 to give the corresponding 3,3-dialkyl saturated lactones (4 and 5). The lactone was constructed from glycidyl-4-methoxyphenyl ether in 5 steps. The target compounds showed reduced binding affinities for PKC-.alpha. with $K_{i}$ values of 192 nM (3), 4,829 nM (4), and 2,812 nM (5), respectively. These results indicate that constrained DAG analogues having a tetrahydro-2-furanone template are effectively discriminated by PKC-(X in terms of the direction of the long alkyl chain connected to the 3-position.n.

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