• 제목/요약/키워드: 12-O-tetradecanoylphorbol 13-acetate

검색결과 74건 처리시간 0.024초

Inhibitory Effects of Opuntia humifusa on 7, 12-Dimethyl-benz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate Induced Two-stage Skin Carcinogenesis

  • Lee, Jin-A;Jung, Bock-Gie;Lee, Bong-Joo
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권9호
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    • pp.4655-4660
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    • 2012
  • Opuntia humifusa, member of the Cactaceae family, was previously demonstrated to have radical scavenging, anti-inflammatory and anti-proliferative effects in in vitro models. It was suggested that O. humifusa could function in the prevention of carcinogenesis. To investigate the in vivo chemopreventive effect of O. humifusa, mice were fed a diet containing either 1% or 3% following 7, 12-dimethylbenz[a] anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induction of skin carcinogenesis. Significant decrease in the numbers of papilloma and epidermal hyperplasia were observed in mice fed with O. humifusa, compared to the control group. O. humifusa also upregulated high total antioxidant capacity and level of phase II detoxifying enzyme such as superoxide dismutase and glutathione S-transferase activity in the skin. Lipid peroxidation activity level was measured in skin cytosol and significantly inhibited in 3% OH fed group compared to the control group. These results suggest that O. humifusa exerts chemopreventive effects on chemical carcinogenesis in mouse skin and that prevention effects are associated with reduction of oxidative stress via the modulation of cutaneous lipid peroxidation, enhancing of total antioxidant capacity especially in phase II detoxifying enzyme system and partial apoptotic influence.

Inhibitory Effect of Kaempferol on Apoptosis Induced by Phorbol Ester via the Reduction of ROS in Normal Human Dermal Fibroblast

  • Park, Su-Ji;Lee, Sei-Jung
    • 한국환경과학회:학술대회논문집
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    • 한국환경과학회 2020년도 정기학술대회 발표논문집
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    • pp.219-219
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    • 2020
  • Kaempferol (3,4',5,7-tetrahydroxyflavone), a flavonoid found in beans, broccoli, garlic, etc., has been used in natural medicine as an anti-inflammatory and antioxidant. This experiment was carried out to evaluate the anti-apoptotic effect of kaempferol in 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated Normal Human Dermal Fibroblast (NHDF). Kaempferol inhibited the production of intracellular Reactive Oxygen Species (ROS) induced by TPA in NHDF. Kaempferol significantly blocks the phosphorylation of extracellular signal-regulated kinase responsible for the activation of nuclear factor-kappa B. In addition, kaempferol significantly attenuated the expression of Bax and cleaved caspase-3 as regulated by the phosphorylation of nuclear factor-kappa B during its blockage of TPA-induced apoptotic cell death. These findings suggest that kaempferol protects the apoptotic signaling pathway induced by TPA through modulating intracellular ROS in NHDF.

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3,3'-Diindolylmethane(DIM)이 Human Mammary Epithelial Cell에서 12-O-tetradecanoylphorbol-13-acetate에 의해 유도된 COX-2 발현에 미치는 영향 (The Effect of 12-O-Tetradecanoylphorbol-13-acetate-induced COX-2 Expression by 3,3'-Diindolylmethane (DIM) on Human Mammary Epithelial Cells)

  • 박소영;심재훈;김종대;윤정한
    • 한국식품영양과학회지
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    • 제41권12호
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    • pp.1701-1707
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    • 2012
  • 3,3'-Diindolylmethane(DIM)은 십자화과 채소에 포함되어 있는 indole-3-carbinol(I3C)이 동물의 산성 위액에서 중합되어 생성된 물질이다. 지금까지 DIM은 유방암, 전립선암 그리고 대장암 세포주에서 항암효과가 있다고 알려져 있으며 그 기작에 대한 연구도 다양하게 진행되고 있다. 그러나 정상세포에서 암화과정 중 암의 촉진과 진행과정의 주요한 항암 표적인 항염증에 대한 연구는 보고된 바 없다. 따라서 본 연구에서는 유방상피세포인 MCF-10A 세포에 12-O-tetradecanoylphorbol-13-acetate(TPA)로 염증반응을 유도한 후 DIM이 염증작용에 미치는 영향을 조사하였다. 그 결과 MCF-10A 세포에서 TPA에 의해 유도된 COX-2 단백질 및 mRNA 발현이 DIM 처리에 의해 현저히 감소하였다. 또한 TPA에 의해 유도된 $I{\kappa}B-{\alpha}$의 분해, p65의 핵으로의 이동, $NF-{\kappa}B$ DNA binding activity 역시 DIM의 처리에 의해 감소하였다. 이는 DIM이 인간의 유방상피세포인 MCF-10A 세포에서 TPA에 의해 유도된 $NF-{\kappa}B$ 신호전달체계의 활성을 억제함으로써 COX-2의 발현을 억제하여 염증반응을 조절함을 나타낸다. 그러므로 이러한 결과들은 DIM을 염증성 질환 예방제 또는 치료제로 개발할 수 있는 가능성을 시사한다.

12-O-Tetradecanoylphorbol-13-Acetate Induces Keratin 8 Phosphorylation and Reorganization via Expression of Transglutaminase-2

  • Lee, Eun Ji;Park, Mi Kyung;Kim, Hyun Ji;Kang, June Hee;Kim, You Ri;Kang, Gyeoung Jin;Byun, Hyun Jung;Lee, Chang Hoon
    • Biomolecules & Therapeutics
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    • 제22권2호
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    • pp.122-128
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    • 2014
  • The stiffness of cancer cells is attributable to intermediate filaments such as keratin. Perinuclear reorganization via phosphorylation of specific serine residue in keratin is implicated in the deformability of metastatic cancer cells including the human pancreatic carcinoma cell line (PANC-1). 12-O-Tetradecanoylphorbol-13-acetate (TPA) is a potent tumor promoter and protein kinase C (PKC) activator. However, its effects on phosphorylation and reorganization of keratin 8 (K8) are not well known. Therefore, we examined the underlying mechanism and effect of TPA on K8 phosphorylation and reorganization. TPA induced phosphorylation and reorganization of K8 and transglutaminase-2 (Tgase-2) expression in a time- and dose-dependent manner in PANC-1 cells. These effects peaked after 45 min and 100 nM of TPA treatment. We next investigated, using cystamine (CTM), Tgase inhibitor, and Tgase-2 gene silencing, Tgase-2's possible involvement in TPA-induced K8 phosphorylation and reorganization. We found that Tgase-2 gene silencing inhibited K8 phosphorylation and reorganization in PANC-1 cells. Tgase-2 gene silencing, we additionally discovered, suppressed TPA-induced migration of PANC-1 cells and Tgase-2 overexpression induced migration of PANC-1 cells. Overall, these results suggested that TPA induced K8 phosphorylation and reorganization via Tgase-2 expression in PANC-1 cells.

Curcumin Suppresses Activation of NF-κB and AP-1 Induced by Phorbol Ester in Cultured Human Promyelocytic Leukemia Cells

  • Han, Seong-Su;Keum, Young-Sam;Seo, Hyo-Joung;Surh, Young-Joon
    • BMB Reports
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    • 제35권3호
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    • pp.337-342
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    • 2002
  • Many components that are derived from medicinal or dietary plants possess potential chemopreventive properties. Curcumin, a yellow coloring agent from turmeric (Curcuma longa Linn, Zingiberaceae), possesses strong antimutagenic and anticarcinogenic activities. In this study, we have found that curcumin inhibits the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear factor ${\kappa}B$ (NF-${\kappa}B$) activation by preventing the degradation of the inhibitory protein $I{\kappa}B{\alpha}$ and the subsequent translocation of the p65 subunit in cultured human promyelocytic leukemia (HL-60) cells. Alternatively, curcumin repressed the TPA-induced activation of NF-${\kappa}B$ through direct interruption of the binding of NF-${\kappa}B$ to its consensus DNA sequences. Likewise, the TPA-induced DNA binding of the activator protein-1 (AP-1) was inhibited by curcumin pretreatment.

Evaluation of the Potential of Cancer Chemopreventive Activity Mediated by Inhibition of 12-O-tetradecanoly Phorbol 13-acetate-induced Ornithine Decarboxylase Activity

  • Lee, Sang-Kook;Pezzuto, John-M.
    • Archives of Pharmacal Research
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    • 제22권6호
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    • pp.559-564
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    • 1999
  • In order to discover new cancer chemopreventive agents from natural or synthetic products, a structurally diverse class of chemopreventive agents was evaluated using in vitro biomarker of inhibition of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity in cultured mouse epidermal 308 (ME)308 cells. As a results, apigenin, benzylisothiocyanate, curcumin, diallyl disulfide, N-(4-hydroxyphenyl)retinamide (4-HPR), menadione, miconazole, nordihydroguaiaretic acid (NDGA) and phenethyl isothiocyanate showed potent inhibitory effects in this process. A chemically diverse group of compounds was included in the evaluation, such as flavonoids, retinoids, isothiocyanates, sulfur-containing compounds and phenolic antioxidant compounds. These data are suggestive to understand the cancer chemopreventive potential mediated by these substances.

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Involvement of P38 Mapk and Gap Junctional Intercellular Communication (Gjic) in 12-O-Tetradecanoyl Phorbol 13-Acetate-Induced Stellation of Neurosphere-Derived Cells

  • Yang, Se-Ran;Ahn, Nam-Shik;Jung, Ji-Won;Park, Joon-Suk;Yoon, Byoung-Su;Lee, Yong-Soon;Kang, Kyung-Sun
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2003년도 추계학술대회
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    • pp.123-123
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    • 2003
  • Primary cultures of rat fetus brain exhibit phenotypes of neuron, oligodendrocyte, and astrocyte from "neurospheres". To understand the role of mitogen-activated protein kinase (MAPK) cascade and gap junctional intercellular communication (GJIC) in the differentiation of neurosphere-derived astrocyte, we investigated the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the cultured astrocyte morphology.(omitted)

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Anti-inflammatory effect of aged black garlic on 12-O-tetradecanoylphorbol-13-acetate-induced dermatitis in mice

  • You, Bo Ram;Yoo, Jae-Myung;Baek, Seong Yeon;Kim, Mee Ree
    • Nutrition Research and Practice
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    • 제13권3호
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    • pp.189-195
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    • 2019
  • BACKGROUND/OBJECTIVES: Although aged black garlic has various biological activities such as anti-allergy, anti-inflammation and neuroprotection, effect of aged black garlic on chemically contact dermatitis is unclarified. MATERIALS/METHODS: To evaluate anti-dermatitic activity of aged black garlic extract, we investigated effects of a fraction of aged black garlic extract (BG10) on both in vivo and in vitro. RESULTS: BG10 almost inhibited formation of nitric monoxide and interleukin-6 (IL-6; $IC_{50}$, $7.07{\mu}g/mL$) at $25{\mu}g/mL$, and dose-dependently reduced production of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$; $IC_{50}$, $52.07{\mu}g/mL$) and prostaglandin $E_2$ ($IC_{50}$, $38.46{\mu}g/mL$) in lipopolysaccharide-stimulated RAW264.7 cells. In addition, BG10 significantly inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear $NF-{\kappa}B$, and improved that of cytosolic levels of $NF-{\kappa}B$ and $I{\kappa}B{\alpha}$ in the cells. Consistent with in vitro studies, BG10 (0.5 mg/mL) not only reduced ear edema but also suppressed the formation of IL-6 and $TNF-{\alpha}$ induced by 12-O-tetradecanoylphorbol-13-acetate in ear tissues of mice. CONCLUSIONS: These findings suggest BG10 has anti-dermatitic activity through inhibiting activation of macrophages. Therefore, such effects of BG10 may provide information for the application of aged black garlic for prevention and therapy of contact dermatitis.

Synthesis and Anti-inflammatory Activity of Fructigenine A Derivatives

  • Chang, Jun-Hwan;Moon, Hong-sik
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제9권1호
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    • pp.59-61
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    • 2004
  • Several derivatives were synthesized from fructigenine A, which was isolated from Penicillium fructigenum. The anti-inflammatory properties of fructigenine A was evaluated in vivo with a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model and a carrageenan-induced rat paw edema model. Results showed that the anti-inflammatory activity was significantly higher with fructigenine derivatives than with indomethacin, which was used as a standard. We concluded that fructigenine derivatives could exert an anti-inflammatory effect.