Compounds > 12-o-tetradeca-2-4-6-8-tetranoylphorbol-13-acetate

12-o-tetradeca-2-4-6-8-tetranoylphorbol-13-acetate and nobiletin

12-o-tetradeca-2-4-6-8-tetranoylphorbol-13-acetate has been researched along with nobiletin* in 1 studies

Other Studies

1 other study(ies) available for 12-o-tetradeca-2-4-6-8-tetranoylphorbol-13-acetate and nobiletin

Article	Year
Activation of protein kinase C betaII/epsilon-c-Jun NH2-terminal kinase pathway and inhibition of mitogen-activated protein/extracellular signal-regulated kinase 1/2 phosphorylation in antitumor invasive activity induced by the polymethoxy flavonoid, nobi Molecular cancer therapeutics, 2004, Volume: 3, Issue:7 Flavonoids from medicinal plants have been therapeutically administered for cancer therapy. We recently reported that nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) exhibits novel antitumor invasive activities by suppressing the production of pro-matrix metalloproteinases (proMMPs) and augmenting the expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo and in vitro. In the present study, intracellular target molecules associated with the actions of nobiletin against tumor invasion were identified. Nobiletin inhibited the phosphorylation of mitogen-activated protein/extracellular signal-regulated kinase (MEK) 1/2, but not the activity of Ras or the phosphorylation of Raf. Moreover, a MEK1/2 inhibitor, U0126, mimicked nobiletin's ability to decrease the production of proMMPs-1 and 9 in human fibrosarcoma HT-1080 cells stimulated by 12-O-tetradecanoyl phorbol-13-acetate (TPA). In addition, neither the activity of phosphatidylinositol 3-kinase (PI3K) nor the phosphorylation of Akt was influenced by nobiletin. However, nobiletin was found to augment the phosphorylation of c-Jun NH2-terminal kinase (JNK), a downstream signal factor of the PI3K-Akt pathway, in TPA-treated HT-1080 cells. A similar augmentation of JNK phosphorylation was observed on treatment with a PI3K inhibitor, LY-294002. Furthermore, nobiletin enhancement of TIMP-1 production in TPA-stimulated HT-1080 cells was found to be diminished by adding a JNK inhibitor, SP600125. Moreover, protein kinase C (PKC) inhibitor experiments showed that PKCbetaII/epsilon were associated with the nobiletin-mediated augmentation of JNK phosphorylation. Therefore, these results introduce novel evidence that the antitumor effects of nobiletin are finely regulated by the following intracellular mechanisms: (1) the inhibition of MEK1/2 activity is involved in the suppression of MMP expression and (2) the activation of the novel PKCbetaII/epsilon-JNK pathway is associated with the augmentation of TIMP-1 expression. Topics: Anthracenes; Antineoplastic Agents; Butadienes; Cell Line, Tumor; Collagenases; Enzyme Activation; Enzyme Precursors; Flavones; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Matrix Metalloproteinase 9; Mitogen-Activated Protein Kinase Kinases; Neoplasm Invasiveness; Nitriles; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Kinase C; Protein Kinase C beta; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; raf Kinases; ras Proteins; Tetradecanoylphorbol Acetate; Tissue Inhibitor of Metalloproteinase-1	2004

Article

Year

Activation of protein kinase C betaII/epsilon-c-Jun NH2-terminal kinase pathway and inhibition of mitogen-activated protein/extracellular signal-regulated kinase 1/2 phosphorylation in antitumor invasive activity induced by the polymethoxy flavonoid, nobi

Molecular cancer therapeutics, 2004, Volume: 3, Issue:7

Flavonoids from medicinal plants have been therapeutically administered for cancer therapy. We recently reported that nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) exhibits novel antitumor invasive activities by suppressing the production of pro-matrix metalloproteinases (proMMPs) and augmenting the expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo and in vitro. In the present study, intracellular target molecules associated with the actions of nobiletin against tumor invasion were identified. Nobiletin inhibited the phosphorylation of mitogen-activated protein/extracellular signal-regulated kinase (MEK) 1/2, but not the activity of Ras or the phosphorylation of Raf. Moreover, a MEK1/2 inhibitor, U0126, mimicked nobiletin's ability to decrease the production of proMMPs-1 and 9 in human fibrosarcoma HT-1080 cells stimulated by 12-O-tetradecanoyl phorbol-13-acetate (TPA). In addition, neither the activity of phosphatidylinositol 3-kinase (PI3K) nor the phosphorylation of Akt was influenced by nobiletin. However, nobiletin was found to augment the phosphorylation of c-Jun NH2-terminal kinase (JNK), a downstream signal factor of the PI3K-Akt pathway, in TPA-treated HT-1080 cells. A similar augmentation of JNK phosphorylation was observed on treatment with a PI3K inhibitor, LY-294002. Furthermore, nobiletin enhancement of TIMP-1 production in TPA-stimulated HT-1080 cells was found to be diminished by adding a JNK inhibitor, SP600125. Moreover, protein kinase C (PKC) inhibitor experiments showed that PKCbetaII/epsilon were associated with the nobiletin-mediated augmentation of JNK phosphorylation. Therefore, these results introduce novel evidence that the antitumor effects of nobiletin are finely regulated by the following intracellular mechanisms: (1) the inhibition of MEK1/2 activity is involved in the suppression of MMP expression and (2) the activation of the novel PKCbetaII/epsilon-JNK pathway is associated with the augmentation of TIMP-1 expression.

Topics: Anthracenes; Antineoplastic Agents; Butadienes; Cell Line, Tumor; Collagenases; Enzyme Activation; Enzyme Precursors; Flavones; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Matrix Metalloproteinase 9; Mitogen-Activated Protein Kinase Kinases; Neoplasm Invasiveness; Nitriles; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Kinase C; Protein Kinase C beta; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; raf Kinases; ras Proteins; Tetradecanoylphorbol Acetate; Tissue Inhibitor of Metalloproteinase-1

2004