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Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells.

Abstract

Epigallocatechin-3-gallate (EGCG), a major component in green tea polyphenols, has been proven to suppress colonic tumorigenesis in animal models and epidemiological studies. As EGCG is retained in the gastrointestinal tract after oral administration, this pharmacokinetics property gives it the potential to function as a chemopreventive agent against colon cancer. In this study, human colorectal carcinoma HT-29 cells were treated with EGCG to examine the anti-proliferative and pro-apoptotic effects of EGCG, as well as the molecular mechanism underlying these effects. Cell viability assay, nuclear staining, DNA fragmentation, caspase assay, cytochrome c release, DiOC6(3) staining, mitogen-activated protein kinases (MAPK) phosphorylation and trypan blue exclusion assays, were utilized to dissect the signaling pathways induced by EGCG. After 36 h treatment, EGCG inhibited HT-29 cell growth with an IC50 of approximately 100 microM. HT-29 cells treated with doses higher than 100 microM showed apparent nuclear condensation and fragmentation, which was confirmed by DNA laddering. Caspase-3 and -9 activation was detected after 12 h treatment, accompanied by mitochondrial transmembrane potential transition and cytochrome c release. Activation of MAPKs was detected as early signaling event elicited by EGCG. Inhibition of c-Jun N-terminal kinase (JNK) pathway showed the involvement of JNK in EGCG-induced cytochrome c release and cell death. EGCG-induced JNK activation was blocked by the antioxidants glutathione and N-acetyl-l-cysteine, suggesting that the cell death signaling was potentially triggered by oxidative stress. In summary, our results from this study suggest that in HT-29 human colon cancer cells (i) EGCG treatment causes damage to mitochondria, and (ii) JNK mediates EGCG-induced apoptotic cell death.

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  • Authors+Show Affiliations

    ,

    Department of Pharmaceutics, Ernest-Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

    , , , ,

    Source

    Carcinogenesis 24:8 2003 Aug pg 1369-78

    MeSH

    Adenocarcinoma
    Anticarcinogenic Agents
    Antioxidants
    Apoptosis
    Blotting, Western
    Caspase 3
    Caspase 9
    Caspases
    Catalase
    Catechin
    Colonic Neoplasms
    Cytochrome c Group
    DNA, Neoplasm
    Enzyme Activation
    Enzyme Inhibitors
    Free Radical Scavengers
    Glutathione
    HT29 Cells
    Humans
    JNK Mitogen-Activated Protein Kinases
    Membrane Potentials
    Mitochondria
    Mitogen-Activated Protein Kinase 1
    Mitogen-Activated Protein Kinases
    Oxidants
    Oxidative Stress
    Phosphorylation
    Urokinase-Type Plasminogen Activator
    p38 Mitogen-Activated Protein Kinases

    Pub Type(s)

    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    12819184

    Citation

    Chen, Chi, et al. "Epigallocatechin-3-gallate-induced Stress Signals in HT-29 Human Colon Adenocarcinoma Cells." Carcinogenesis, vol. 24, no. 8, 2003, pp. 1369-78.
    Chen C, Shen G, Hebbar V, et al. Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells. Carcinogenesis. 2003;24(8):1369-78.
    Chen, C., Shen, G., Hebbar, V., Hu, R., Owuor, E. D., & Kong, A. N. (2003). Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells. Carcinogenesis, 24(8), pp. 1369-78.
    Chen C, et al. Epigallocatechin-3-gallate-induced Stress Signals in HT-29 Human Colon Adenocarcinoma Cells. Carcinogenesis. 2003;24(8):1369-78. PubMed PMID: 12819184.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells. AU - Chen,Chi, AU - Shen,Guoxiang, AU - Hebbar,Vidya, AU - Hu,Rong, AU - Owuor,Edward D, AU - Kong,A-N Tony, Y1 - 2003/06/19/ PY - 2003/6/24/pubmed PY - 2003/9/17/medline PY - 2003/6/24/entrez SP - 1369 EP - 78 JF - Carcinogenesis JO - Carcinogenesis VL - 24 IS - 8 N2 - Epigallocatechin-3-gallate (EGCG), a major component in green tea polyphenols, has been proven to suppress colonic tumorigenesis in animal models and epidemiological studies. As EGCG is retained in the gastrointestinal tract after oral administration, this pharmacokinetics property gives it the potential to function as a chemopreventive agent against colon cancer. In this study, human colorectal carcinoma HT-29 cells were treated with EGCG to examine the anti-proliferative and pro-apoptotic effects of EGCG, as well as the molecular mechanism underlying these effects. Cell viability assay, nuclear staining, DNA fragmentation, caspase assay, cytochrome c release, DiOC6(3) staining, mitogen-activated protein kinases (MAPK) phosphorylation and trypan blue exclusion assays, were utilized to dissect the signaling pathways induced by EGCG. After 36 h treatment, EGCG inhibited HT-29 cell growth with an IC50 of approximately 100 microM. HT-29 cells treated with doses higher than 100 microM showed apparent nuclear condensation and fragmentation, which was confirmed by DNA laddering. Caspase-3 and -9 activation was detected after 12 h treatment, accompanied by mitochondrial transmembrane potential transition and cytochrome c release. Activation of MAPKs was detected as early signaling event elicited by EGCG. Inhibition of c-Jun N-terminal kinase (JNK) pathway showed the involvement of JNK in EGCG-induced cytochrome c release and cell death. EGCG-induced JNK activation was blocked by the antioxidants glutathione and N-acetyl-l-cysteine, suggesting that the cell death signaling was potentially triggered by oxidative stress. In summary, our results from this study suggest that in HT-29 human colon cancer cells (i) EGCG treatment causes damage to mitochondria, and (ii) JNK mediates EGCG-induced apoptotic cell death. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/12819184/Epigallocatechin_3_gallate_induced_stress_signals_in_HT_29_human_colon_adenocarcinoma_cells_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgg091 DB - PRIME DP - Unbound Medicine ER -