21 results on '"Li, Jingxia"'
Search Results
2. Abstract 785: The inhibitory effect of compound ChlA-F onhuman bladder cancer cell invasion can be attributed to its blockage of SOX2 protein
- Author
-
Hua, Xiaohui, primary, Xu, Jiheng, additional, Huang, Chuanshu, additional, Li, Jingxia, additional, Tian, Zhongxian, additional, and Huang, Haishan, additional
- Published
- 2019
- Full Text
- View/download PDF
3. Abstract 2306: Transcriptional and post-transcriptional upregulation of p27 mediates growth inhibition of isorhapontigenin/ISO on human bladder cancer cells
- Author
-
Xu, Jiheng, primary, Li, Jingxia, additional, Huang, Chuanshu, additional, Huang, Haishan, additional, and Jiang, Guosong, additional
- Published
- 2018
- Full Text
- View/download PDF
4. Abstract 1062: Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer
- Author
-
Tian, Zhongxian, primary, Jin, Honglei, additional, Li, Jingxia, additional, Huang, Chao, additional, and Huang, Chuanshu, additional
- Published
- 2018
- Full Text
- View/download PDF
5. Abstract 3305: Autophagic induction through upregulation of sestrin-2 transcription and mRNA stability mediates the anticancer effect of new compound ChlA-F
- Author
-
Hua, Xiaohui, primary, Huang, Chuanshu, additional, Wu, Xueru, additional, and Li, Jingxia, additional
- Published
- 2017
- Full Text
- View/download PDF
6. Abstract 533: XIAP BIR domain suppresses miR-200a expression and subsequently promotes EGFR protein translation and anchorage-independent growth of bladder cancer cell
- Author
-
Liao, Xin, primary, Huang, Chao, additional, Li, Jingxia, additional, and Huang, Chuanshu, additional
- Published
- 2017
- Full Text
- View/download PDF
7. Abstract 526: NFκB p65 overexpression promotes bladder cancer migration via FBW7-mediated degradation of RhoGDIα protein
- Author
-
Li, Yang, primary, Zhu, Junlan, additional, Li, Jingxia, additional, and Huang, Chuanshu, additional
- Published
- 2017
- Full Text
- View/download PDF
8. Abstract 1898: MEG3 as a competing endogenous RNA binds with miR-27a to promote PHLPP2 protein translation, and consequently impairs bladder cancer invasion
- Author
-
Huang, Chao, primary, Liao, Xin, additional, Li, Jingxia, additional, and Huang, Chuanshu, additional
- Published
- 2017
- Full Text
- View/download PDF
9. Abstract 5107: Divergent behaviors and underlying mechanisms of cell migration and invasion in non-metastatic T24 and its metastatic derivative T24T bladder cancer cell lines
- Author
-
Jin, Honglei, primary, Li, Jingxia, additional, and Huang, Chuanshu, additional
- Published
- 2015
- Full Text
- View/download PDF
10. Abstract 4641: Crucial role of c-Jun phosphorylation at Ser63/73 mediated by PHLPP protein degradation in the Cheliensisin A (Chel A) inhibition of cell transformation
- Author
-
Huang, Chuanshu, primary, Zhu, Junlan, additional, and Li, Jingxia, additional
- Published
- 2015
- Full Text
- View/download PDF
11. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.
- Author
-
Jiang G, Wu AD, Huang C, Gu J, Zhang L, Huang H, Liao X, Li J, Zhang D, Zeng X, Jin H, Huang H, and Huang C
- Subjects
- Animals, Cell Line, Tumor, Cell Movement drug effects, Forkhead Box Protein O1 drug effects, Forkhead Box Protein O1 metabolism, Humans, Interferon-Stimulated Gene Factor 3 drug effects, Interferon-Stimulated Gene Factor 3 metabolism, Matrix Metalloproteinase 2 drug effects, Matrix Metalloproteinase 2 metabolism, Mice, Mice, Inbred C57BL, Random Allocation, Antineoplastic Agents pharmacology, Neoplasm Invasiveness pathology, Signal Transduction drug effects, Stilbenes pharmacology, Urinary Bladder Neoplasms pathology
- Abstract
Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR., (©2016 American Association for Cancer Research.)
- Published
- 2016
- Full Text
- View/download PDF
12. Crucial role of c-Jun phosphorylation at Ser63/73 mediated by PHLPP protein degradation in the cheliensisin a inhibition of cell transformation.
- Author
-
Zhu J, Zhang J, Huang H, Li J, Yu Y, Jin H, Li Y, Deng X, Gao J, Zhao Q, and Huang C
- Subjects
- Animals, Blotting, Western, Cell Proliferation, Cell Transformation, Neoplastic pathology, Cells, Cultured, Epidermal Cells, Epidermal Growth Factor pharmacology, Epidermis metabolism, Flow Cytometry, Immunoprecipitation, Mice, Phosphorylation drug effects, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Serine metabolism, Tumor Suppressor Protein p53 metabolism, Cell Transformation, Neoplastic drug effects, Epidermis drug effects, Epoxy Compounds pharmacology, Nuclear Proteins metabolism, Phosphoprotein Phosphatases metabolism, Proteolysis drug effects, Proto-Oncogene Proteins c-jun metabolism, Pyrones pharmacology, Signal Transduction drug effects
- Abstract
Cheliensisin A (Chel A), as a novel styryl-lactone isolated from Goniothalamus cheliensis Hu, has been demonstrated to have an inhibition of EGF-induced Cl41 cell transformation via stabilizing p53 protein in a Chk1-dependent manner, suggesting its chemopreventive activity in our previous studies. However, its underlying molecular mechanisms have not been fully characterized yet. In the current study, we found that Chel A treatment could increase c-Jun protein phosphorylation and activation, whereas the inhibition of c-Jun phosphorylation, by ectopic expression of a dominant-negative mutant of c-Jun, TAM67, reversed the Chel A inhibition of EGF-induced cell transformation and impaired Chel A induction of p53 protein and apoptosis. Moreover, our results indicated that Chel A treatment led to a PHLPP downregulation by promoting PHLPP protein degradation. We also found that PHLPP could interact with and bind to c-Jun protein, whereas ectopic PHLPP expression blocked c-Jun activation, p53 protein and apoptotic induction by Chel A, and further reversed the Chel A inhibition of EGF-induced cell transformation. With the findings, we have demonstrated that Chel A treatment promotes a PHLPP protein degradation, which can bind to c-Jun and mediates c-Jun phosphorylation, and further leading to p53 protein induction, apoptotic responses, subsequently resulting in cell transformation inhibition and chemopreventive activity of Chel A., (©2014 American Association for Cancer Research.)
- Published
- 2014
- Full Text
- View/download PDF
13. Cheliensisin A inhibits EGF-induced cell transformation with stabilization of p53 protein via a hydrogen peroxide/Chk1-dependent axis.
- Author
-
Zhang J, Gao G, Chen L, Deng X, Li J, Yu Y, Zhang D, Li F, Zhang M, Zhao Q, and Huang C
- Subjects
- Animals, Apoptosis drug effects, Blotting, Western, Cell Proliferation drug effects, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Cells, Cultured, Checkpoint Kinase 1, Epidermal Cells, Epidermis metabolism, Flow Cytometry, Humans, Mice, Oxidants pharmacology, Phosphorylation drug effects, Proteolysis drug effects, RNA, Messenger genetics, Reactive Oxygen Species metabolism, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction drug effects, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Cell Transformation, Neoplastic drug effects, Epidermal Growth Factor pharmacology, Epidermis drug effects, Epoxy Compounds pharmacology, Hydrogen Peroxide pharmacology, Protein Kinases metabolism, Protein Stability drug effects, Pyrones pharmacology, Tumor Suppressor Protein p53 chemistry
- Abstract
Cheliensisin A (Chel A), a novel styryl-lactone isolated from Goniothalamus cheliensis Hu, has been shown to induce apoptosis in human promyelocytic leukemia HL-60 cells with Bcl-2 downregulation. Yet, the potential chemopreventive effect of Chel A has not been explored. Here, we showed that Chel A treatment with various concentrations (0.5, 1.0, 2.0, and 4.0 μmol/L) for 3 weeks could dramatically inhibit EGF-induced cell transformation in Cl41 cells (IC50 ∼2.0 μmol/L). Also, coincubation of Cl41 cells with Chel A (2.0 and 4.0 μmol/L) for 48 hours could induce cell apoptosis in a caspase-3-dependent manner. Mechanically, Chel A treatment could result in increased p53 phosphorylation at Ser15 and elevated p53 total protein expression. Moreover, we found that p53 induction by Chel A was regulated at the protein degradation level, but not at either the transcription or the mRNA level. Further studies showed that p53 stabilization by Chel A was mediated via induction of phosphorylation and activation of Chk1 protein at Ser345. This notion was substantiated by the results that transfection of dominant negative mutant of Chk1 (GFP-Chk1 D130A) significantly attenuated the p53 protein expression, cell apoptosis, and inhibition of cell transformation by Chel A. Finally, increased hydrogen peroxide was found to mediate Chk1 phosphorylation at Ser345, p53 protein induction, cell apoptotic induction, and transformation inhibition following Chel A treatment. Taken together, our studies identify Chel A as a chemopreventive agent with the understanding of the molecular mechanisms involved.
- Published
- 2013
- Full Text
- View/download PDF
14. JNK1 mediates degradation HIF-1alpha by a VHL-independent mechanism that involves the chaperones Hsp90/Hsp70.
- Author
-
Zhang D, Li J, Costa M, Gao J, and Huang C
- Subjects
- Animals, Carcinogens toxicity, Cell Hypoxia physiology, Cell Line, Tumor, HeLa Cells, Histone Deacetylase 6, Histone Deacetylases biosynthesis, Humans, Hypoxia-Inducible Factor 1, alpha Subunit biosynthesis, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Mice, Mitogen-Activated Protein Kinase 8 genetics, Nickel toxicity, RNA, Messenger biosynthesis, RNA, Messenger genetics, Transcriptional Activation, Transfection, Von Hippel-Lindau Tumor Suppressor Protein metabolism, HSP70 Heat-Shock Proteins metabolism, HSP90 Heat-Shock Proteins metabolism, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Mitogen-Activated Protein Kinase 8 metabolism
- Abstract
Hypoxia-inducible factor-1alpha (HIF-1alpha) is a master transcription factor that is critical for the regulation of a variety of cellular functions. HIF-1alpha is rapidly degraded under normoxic conditions by ubiquitin-mediated proteasome pathway controlled by the tumor suppressor von Hippel Lindau (VHL). Several recent studies reveal that heat-shock proteins (Hsp) can regulate HIF-1alpha protein degradation by a VHL-independent pathway. Here, we demonstrate that the stress kinase c-Jun NH(2)-terminal kinase 1 (JNK1) is required for Hsp-dependent regulation of HIF-1alpha. Stabilization of HIF-1alpha was impaired in JNK1-/- cells but could be rescued by JNK1 reconstitution under hypoxic conditions. These effects could be phenocopied in other cell settings by JNK1 silencing. Accordingly, HIF-1 transcriptional activity and target gene expression were dramatically reduced in JNK1-/- cells. Further, decreased levels of endogenous Hsp90/Hsp70 proteins in JNK1-/- cells affected the protective roles of these chaperones in stabilizing newly synthesized HIF-1alpha, whereas enforced expression of Hsp90/Hsp70 in JNK1-/- cells increased HIF-1alpha stability relative to parental control cells. Furthering this connection, we also found that defective expression of the Hsp90 acetyltransferase HDAC6 in JNK1-/- cells was associated with reduced Hsp90 chaperone activity. Taken together, our studies define a novel function for JNK1 in regulating HIF-1alpha turnover by a VHL-independent mechanism.
- Published
- 2010
- Full Text
- View/download PDF
15. A JNK1/AP-1-dependent, COX-2 induction is implicated in 12-O-tetradecanoylphorbol-13-acetate-induced cell transformation through regulating cell cycle progression.
- Author
-
Zhang D, Li J, Song L, Ouyang W, Gao J, and Huang C
- Subjects
- Animals, Enzyme Induction drug effects, Fibroblasts cytology, Fibroblasts drug effects, Fibroblasts enzymology, Humans, I-kappa B Kinase metabolism, Mice, Mitogen-Activated Protein Kinase 9 metabolism, Transcription Factor RelA metabolism, Cell Cycle drug effects, Cell Transformation, Neoplastic drug effects, Cyclooxygenase 2 biosynthesis, Mitogen-Activated Protein Kinase 8 metabolism, Tetradecanoylphorbol Acetate pharmacology, Transcription Factor AP-1 metabolism
- Abstract
Cyclooxygenase-2 (COX-2) is reported to be one of the early-response gene products induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the relevance of COX-2 in TPA-induced cell transformation and the underlying mechanisms remains to be explored. Initially, we verified COX-2 induction after TPA treatment in mouse embryonic fibroblasts (MEF) and mouse epidermal cells Cl 41. More importantly, introduction of COX-2 small interfering RNA in MEFs or Cl 41 cells suppressed the cell transformation caused by TPA treatment. This inhibition could be reversed by overexpression of human full-length COX-2, indicating that COX-2 is at least one of the critical molecules involved in TPA-induced cell transformation. We further showed that TPA-promoted cell cycle progression was partially suppressed by COX-2 small interfering RNA, indicating that COX-2 also participated in TPA-associated cell cycle progression. Investigation of the upstream signaling pathways revealed that c-Jun-NH(2)-kinase 1 (JNK1), but not JNK2, played important roles in COX-2 induction, because knockout of JNK1 gene rather than JNK2 gene markedly impaired COX-2 induction. Furthermore, inhibition of c-Jun/activator protein 1 pathway or JNKs/c-Jun pathway by overexpression of dominant negative mutants of c-Jun, or MKK4 and MKK7 together, resulted in impairment of COX-2 induction, suggesting that JNK1/c-Jun/activator protein 1 pathway is involved in TPA-associated COX-2 induction. In contrast, IKK/p65 nuclear factor-kappaB pathway was not implicated because knockout of IKKalpha, IKKbeta, or p65 gene did not affect COX-2 induction although nuclear factor-kappaB was activated by TPA. In addition, the TPA-promoted cell cycle progression was found impaired in JNK1-deficient, but not in JNK2-deficient, MEFs. Our results show that JNK1-associated COX-2 induction is implicated in TPA-associated cell transformation and cell cycle progression.
- Published
- 2008
- Full Text
- View/download PDF
16. Black raspberry extracts inhibit benzo(a)pyrene diol-epoxide-induced activator protein 1 activation and VEGF transcription by targeting the phosphotidylinositol 3-kinase/Akt pathway.
- Author
-
Huang C, Li J, Song L, Zhang D, Tong Q, Ding M, Bowman L, Aziz R, and Stoner GD
- Subjects
- 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide pharmacology, Animals, Carcinogens pharmacology, Cricetinae, Enzyme Induction, Mice, Nitric Oxide Synthase Type II biosynthesis, Nitric Oxide Synthase Type II genetics, Ribosomal Protein S6 Kinases, 70-kDa biosynthesis, Ribosomal Protein S6 Kinases, 70-kDa genetics, Ribosomal Protein S6 Kinases, 70-kDa metabolism, Transcription Factor AP-1 biosynthesis, Transcription Factor AP-1 genetics, Transcription, Genetic, Vascular Endothelial Growth Factor A biosynthesis, Vascular Endothelial Growth Factor A genetics, Fruit, Phosphatidylinositol 3-Kinases metabolism, Plant Extracts pharmacology, Proto-Oncogene Proteins c-akt metabolism, Rosaceae, Transcription Factor AP-1 antagonists & inhibitors, Vascular Endothelial Growth Factor A antagonists & inhibitors
- Abstract
Previous studies have shown that freeze-dried black raspberry extract fractions inhibit benzo(a)pyrene [B(a)P]-induced transformation of Syrian hamster embryo cells and benzo(a)pyrene diol-epoxide [B(a)PDE]-induced activator protein-1 (AP-1) activity in mouse epidermal Cl 41 cells. The phosphotidylinositol 3-kinase (PI-3K)/Akt pathway is critical for B(a)PDE-induced AP-1 activation in mouse epidermal Cl 41 cells. In the present study, we determined the potential involvement of PI-3K and its downstream kinases on the inhibition of AP-1 activation by black raspberry fractions, RO-FOO3, RO-FOO4, RO-ME, and RO-DM. In addition, we investigated the effects of these fractions on the expression of the AP-1 target genes, vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). Pretreatment of Cl 41 cells with fractions RO-F003 and RO-ME reduced activation of AP-1 and the expression of VEGF, but not iNOS. In contrast, fractions RO-F004 and RO-DM had no effect on AP-1 activation or the expression of either VEGF or iNOS. Consistent with inhibition of AP-1 activation, the RO-ME fraction markedly inhibited activation of PI-3K, Akt, and p70 S6 kinase (p70(S6k)). In addition, overexpression of the dominant negative PI-3K mutant delta p85 reduced the induction of VEGF by B(a)PDE. It is likely that the inhibitory effects of fractions RO-FOO3 and RO-ME on B(a)PDE-induced AP-1 activation and VEGF expression are mediated by inhibition of the PI-3K/Akt pathway. In view of the important roles of AP-1 and VEGF in tumor development, one mechanism for the chemopreventive activity of black raspberries may be inhibition of the PI-3K/Akt/AP-1/VEGF pathway.
- Published
- 2006
- Full Text
- View/download PDF
17. Cyclin D1 induction through IkappaB kinase beta/nuclear factor-kappaB pathway is responsible for arsenite-induced increased cell cycle G1-S phase transition in human keratinocytes.
- Author
-
Ouyang W, Ma Q, Li J, Zhang D, Liu ZG, Rustgi AK, and Huang C
- Subjects
- Animals, Cyclin D1 genetics, G1 Phase drug effects, G1 Phase physiology, Humans, I-kappa B Kinase antagonists & inhibitors, I-kappa B Kinase genetics, Keratinocytes cytology, Keratinocytes enzymology, Mice, Mice, Knockout, S Phase drug effects, S Phase physiology, Transfection, Arsenites pharmacology, Cyclin D1 biosynthesis, I-kappa B Kinase metabolism, Keratinocytes drug effects, Keratinocytes metabolism, NF-kappa B metabolism
- Abstract
Environmental and occupational exposure to arsenite is associated with an increased risk of human cancers, including skin, urinary bladder, and respiratory tract cancers. Although much evidence suggests that alterations in cell cycle machinery are implicated in the carcinogenic effect of arsenite, the molecular mechanisms underlying the cell cycle alterations are largely unknown. In the present study, we observed that exposure of human keratinocyte HaCat cells to arsenite resulted in the promotion of cell cycle progression, especially G(1)-S transition. Further studies found that arsenite exposure was able to induce cyclin D1 expression. The induction of cyclin D1 by arsenite required nuclear factor-kappaB (NF-kappaB) activation, because the inhibition of IkappaB phosphorylation by overexpression of the dominant-negative mutant, IKKbeta-KM, impaired arsenite-induced cyclin D1 expression and G1-S transition. The requirement of IkappaB kinase beta (IKKbeta) for cyclin D1 induction was further confirmed by the findings that arsenite-induced cyclin D1 expression was totally blocked in IKKbeta knockout (IKKbeta(-/-)) mouse embryo fibroblasts. In addition, knockdown of cyclin D1 expression using cyclin D1-specific small interference RNA significantly blocked arsenite-induced cell cycle progression in HaCat cells. Taken together, our results show that arsenite-induced cell cycle from G(1) to S phase transition is through IKKbeta/NF-kappaB/cyclin D1-dependent pathway.
- Published
- 2005
- Full Text
- View/download PDF
18. Loss of tumor suppressor p53 decreases PTEN expression and enhances signaling pathways leading to activation of activator protein 1 and nuclear factor kappaB induced by UV radiation.
- Author
-
Wang J, Ouyang W, Li J, Wei L, Ma Q, Zhang Z, Tong Q, He J, and Huang C
- Subjects
- Animals, Benzothiazoles, Cell Line, Down-Regulation, Epidermis enzymology, JNK Mitogen-Activated Protein Kinases metabolism, MAP Kinase Signaling System, Mice, NF-kappa B radiation effects, PTEN Phosphohydrolase, Phosphorylation radiation effects, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-akt, RNA, Small Interfering genetics, Ribosomal Protein S6 Kinases, 70-kDa metabolism, Thiazoles pharmacology, Toluene analogs & derivatives, Toluene pharmacology, Transcription Factor AP-1 radiation effects, Transfection, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 physiology, Ultraviolet Rays, p38 Mitogen-Activated Protein Kinases metabolism, NF-kappa B physiology, Phosphoric Monoester Hydrolases biosynthesis, Transcription Factor AP-1 physiology, Tumor Suppressor Protein p53 antagonists & inhibitors, Tumor Suppressor Proteins biosynthesis
- Abstract
Transcription factor p53 and phosphatase PTEN are two tumor suppressors that play essential roles in suppression of carcinogenesis. However, the mechanisms by which p53 mediates anticancer activity and the relationship between p53 and PTEN are not well understood. In the present study, we found that pretreatment of mouse epidermal Cl41 cells with pifithrin-alpha, an inhibitor for p53-dependent transcriptional activation, resulted in a marked increase in UV-induced activation of activator protein 1 (AP-1) and nuclear factor kappaB (NF-kappaB). Consistent with activation of AP-1 and NF-kappaB, pifithrin-alpha was also able to enhance the UV-induced phosphorylation of c-Jun-NH2-kinases (JNK) and p38 kinase, whereas it did not show any effect on phosphorylation of extracellular signal-regulated kinases. Furthermore, the UV-induced signal activation, including phosphorylation of JNK, p38 kinase, Akt, and p70S6K, was significantly enhanced in p53-deficient cells (p53-/-), which can be reversed by p53 reconstitution. In addition, knockdown of p53 expression by its small interfering RNA also caused the elevation of AP-1 activation and Akt phosphorylation induced by UV radiation. These results show that p53 has a suppressive activity on the cell signaling pathways leading to activation of AP-1 and NF-kappaB in cell response to UV radiation. More importantly, deficiency of p53 expression resulted in a decrease in PTEN protein expression, suggesting that p53 plays a critical role in the regulation of PTEN expression. In addition, overexpression of wild-type PTEN resulted in inhibition of UV-induced AP-1 activity. Because PTEN is a well-known phosphatase involved in the regulation of phosphatidylinositol 3-kinase (PI-3K)/Akt signaling pathway, taken together with the evidence that PI-3K/Akt plays an important role in the activation of AP-1 and NF-kappaB during tumor development, we anticipate that inhibition of AP-1 and NF-kappaB by tumor suppressor p53 seems to be mediated via PTEN, which may be a novel mechanism involved in anticancer activity of p53 protein.
- Published
- 2005
- Full Text
- View/download PDF
19. Nickel compounds act through phosphatidylinositol-3-kinase/Akt-dependent, p70(S6k)-independent pathway to induce hypoxia inducible factor transactivation and Cap43 expression in mouse epidermal Cl41 cells.
- Author
-
Li J, Davidson G, Huang Y, Jiang BH, Shi X, Costa M, and Huang C
- Subjects
- 3T3 Cells, Animals, Carcinogens toxicity, Cell Cycle Proteins, Cell Line, Enzyme Activation drug effects, Hypoxia-Inducible Factor 1, alpha Subunit, Intracellular Signaling Peptides and Proteins, Mice, Mice, Inbred BALB C, Proteins genetics, Transcriptional Activation drug effects, Transfection, Epidermis physiology, Nickel toxicity, Phosphatidylinositol 3-Kinases metabolism, Ribosomal Protein S6 Kinases, 70-kDa metabolism, Transcription Factors genetics
- Abstract
Nickel compounds are a somewhat unique class of carcinogens. Previous studies have demonstrated that NiCl(2) exposure leads to marked induction of hypoxia inducible factor 1 (HIF-1) in human osteosarcoma and BALB/c 3T3 cells, a transcription factor that has been considered to play an important role in tumor promotion and progression. However, the signal transduction pathways leading to HIF-1 induction are not well understood. The present study indicated that exposure of mouse epidermal Cl41 cells to either Ni(3)S(2) or NiCl(2) resulted in activation of phosphatidylinositol 3-kinase (PI-3K), Akt, and p70 S6 kinase (p70(S6k)). Inhibition of PI-3K, Akt, and p70(S6k) by overexpression of a dominant-negative mutant of PI-3K (Deltap85) impaired nickel-induced HIF-1 transactivation. Furthermore, an overexpression of the dominant-negative Akt mutant (Akt-T308A/S473A) blocked nickel-induced Akt phosphorylation and HIF-1 transactivation, whereas inhibition of p70(S6k) activation by pretreatment of cells with rapamycin did not show significant inhibitory effects on HIF-1 transactivation induced by nickel compounds. Consistent with HIF-1 transactivation, inhibition of the PI-3K/Akt pathway by either overexpression of Deltap85 or Akt-T308A/S473A caused dramatic inhibition of Cap43 protein expression induced by nickel compounds, whereas pretreatment of cells with rapamycin did not exhibit inhibition of Cap43 induction. These results demonstrated that nickel compounds induce HIF-1 transactivation and Cap43 protein expression through a PI-3K/Akt-dependent and p70(S6k)-independent pathway. This study should help us understand the signal transduction pathways involved in the carcinogenic effects of nickel compounds.
- Published
- 2004
- Full Text
- View/download PDF
20. Inhibition of benzo(a)pyrene diol-epoxide-induced transactivation of activated protein 1 and nuclear factor kappaB by black raspberry extracts.
- Author
-
Huang C, Huang Y, Li J, Hu W, Aziz R, Tang MS, Sun N, Cassady J, and Stoner GD
- Subjects
- Animals, Carcinogens toxicity, Cell Line, DNA Adducts biosynthesis, Drug Interactions, Enzyme Activation drug effects, Epidermal Cells, Epidermis drug effects, Epidermis physiology, Fruit chemistry, I-kappa B Proteins metabolism, Methanol chemistry, Mice, Mitogen-Activated Protein Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinases metabolism, NF-KappaB Inhibitor alpha, NF-kappa B biosynthesis, NF-kappa B physiology, Phosphorylation drug effects, Plant Extracts pharmacology, Transcription Factor AP-1 physiology, 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide toxicity, Carcinogens antagonists & inhibitors, NF-kappa B antagonists & inhibitors, Rosaceae chemistry, Transcription Factor AP-1 antagonists & inhibitors, Transcriptional Activation drug effects
- Abstract
Freeze-dried black raspberries have been shown to inhibit the development of chemically induced esophageal and colon cancer in rodents. In addition, organic extracts of black raspberries inhibit benzo(a)pyrene (BaP)-induced cell transformation in vitro. The molecular mechanisms through which black raspberries inhibit carcinogenesis remain unclear. We investigated the effects of black raspberry extracts on transactivation of activated protein 1 (AP-1) and nuclear factor kappaB (NFkappaB) induced by BaP diol-epoxide (BPDE), the ultimate carcinogen of BaP, in mouse epidermal JB6 Cl 41 (Cl 41) cells. Black raspberries were extracted with methanol, and the methanol extract was partitioned and chromatographed into several fractions designated RU-F003, RU-F004, RU-DM, and RU-ME. Pretreatment of Cl 41 cells with RU-F003, RU-DM, or RU-ME resulted in an inhibition of BPDE-induced AP-1 and NFkappaB activities. The RU-ME fraction was the most potent inhibitor among the fractions tested. In contrast, fraction RU-F004 did not inhibit BPDE-induced AP-1 or NFkappaB activities in Cl 41 cells. The inhibitory effects of RU-ME on BPDE-induced activation of AP-1 and NFkappaB appear to be mediated via inhibition of mitogen activated protein kinase activation and inhibitory subunit kappaB phosphorylation, respectively. Pretreatment of cells with berry fractions did not result in an inhibition of BPDE binding to DNA; thus, this was not a mechanism of reduced AP-1 and NFkappaB activities. None of the fractions was found to affect p53-dependent transcription activity. In view of the important roles of AP-1 and NFkappaB in tumor promotion/progression, these results suggest that the ability of black raspberries to inhibit tumor development may be mediated by impairing signal transduction pathways leading to activation of AP-1 and NFkappaB. The RU-ME fraction appears to be the major fraction responsible for the inhibitory activity of black raspberries.
- Published
- 2002
21. Ultraviolet-induced phosphorylation of p70(S6K) at Thr(389) and Thr(421)/Ser(424) involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C.
- Author
-
Huang C, Li J, Ke Q, Leonard SS, Jiang BH, Zhong XS, Costa M, Castranova V, and Shi X
- Subjects
- Animals, Cells, Cultured, Electron Spin Resonance Spectroscopy, Enzyme Induction radiation effects, Mice, Phosphorylation radiation effects, Proto-Oncogene Proteins c-akt, Reactive Oxygen Species metabolism, Ribosomal Protein S6 Kinases, 70-kDa biosynthesis, Serine metabolism, Signal Transduction radiation effects, Skin cytology, Skin metabolism, Skin radiation effects, TOR Serine-Threonine Kinases, Threonine metabolism, Ultraviolet Rays, Hydrogen Peroxide metabolism, Protein Kinase C metabolism, Protein Kinases metabolism, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins metabolism, Ribosomal Protein S6 Kinases, 70-kDa metabolism
- Abstract
The p70 S6 kinase (p70(S6k)) is a Ser/Thr kinase that plays an important role in cell growth, transformation, and the transition of the cell cycle in mammalian cells. Because UV radiation has been reported to induce activation of p70(S6k), which is believed to play some role in the carcinogenic effects of sun exposure, the present study investigated the signaling pathways involved in this activation induced by UV radiation in mouse epidermal JB6 Cl41 cells. Exposure of cells to UV radiation led to marked increases in p70(S6k) activity and phosphorylation at Thr(389) and Thr(421)/Ser(424). UV radiation also generated reactive oxygen species as measured by electron spin resonance and by H(2)O(2) and O( minus sign, dot below )(2) fluorescence staining assays in JB6 Cl 41 cells. The scavenging of UV-generated H(2)O(2) by N-acety-L-cyteine (a general antioxidant) or catalase (a specific H(2)O(2) scavenger) inhibited p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424), whereas pretreatment of cells with sodium formate (an.OH radical scavenger) or superoxide dismutase (an O( minus sign, dot below )(2) radical scavenger) did not show any inhibitory effects. Importantly, UV-induced increases in p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424) were dramatically inhibited by pretreatment of cells with rapamycin, LY294002, or PD98059, whereas overexpression of dominant-negative mutants of PKClambda/iota and Akt1 did not inhibit p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424). These results demonstrated that H(2)O(2), phosphatidylinositol 3-kinase, and mammalian target of rapamycin were important players for UV-induced p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424), whereas Akt and atypical protein kinase C were not involved in this activation. The role of H(2)O(2) in p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424) was further supported by the findings that treatment of cells with H(2)O(2) also caused p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424).
- Published
- 2002
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.