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Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells.
Carcinogenesis 2003; 24(8):1369-78C

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.

Authors+Show Affiliations

Department of Pharmaceutics, Ernest-Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -