Mechanism of Action of (−)-Epigallocatechin-3-Gallate: Auto-oxidation–Dependent Inactivation of Epidermal Growth Factor Receptor and Direct Effects on Growth Inhibition in Human Esophageal Cancer KYSE 150 Cells
| Autor: | Zhe Hou, Jungil Hong, Mao-Jung Lee, Hui You, Shengmin Sang, Khew-Voon Chin, Chung S. Yang |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
medicine.medical_specialty Esophageal Neoplasms Receptor ErbB-2 Cell Growth Processes Biology complex mixtures Catechin Superoxide dismutase chemistry.chemical_compound Drug Stability Phenols Cell Line Tumor Gallic Acid Internal medicine medicine Biflavonoids Humans Benzopyrans heterocyclic compounds Epidermal growth factor receptor Phosphorylation Superoxide Dismutase Cell growth Superoxide food and beverages Molecular biology ErbB Receptors Endocrinology Oncology Mechanism of action chemistry Cell culture Carcinoma Squamous Cell biology.protein sense organs medicine.symptom Growth inhibition Oxidation-Reduction A431 cells |
| Zdroj: | Cancer Research. 65:8049-8056 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-05-0480 |
| Popis: | (−)-Epigallocatechin-3-gallate (EGCG), the principal polyphenol in green tea, has been shown to inhibit the growth of many cancer cell lines and to suppress the phosphorylation of epidermal growth factor receptor (EGFR). We observed similar effects of EGCG in esophageal squamous cell carcinoma KYSE 150 cells and epidermoid squamous cell carcinoma A431 cells. Pretreatment of KYSE 150 cells with EGCG (20 μmol/L) for 0.5 to 24 hours in HAM's F12 and RPMI 1640 mixed medium at 37°C, before the addition of EGF, resulted in a decreased level of phosphorylated EGFR (by 32-85%). Prolonged treatment with EGCG (8 or 24 hours) also decreased EGFR protein level (both by 80%). EGCG treatment for 24 hours also caused decreased signals of HER-2/neu in esophageal adenocarcinoma OE19 cells. These effects of EGCG were prevented or diminished by the addition of superoxide dismutase (SOD, 5 units/mL), or SOD plus catalase (30 units/mL), to the cell culture medium. A similar phenomenon on inactivation of EGFR was observed in A431 cells as well. Under culture conditions for KYSE 150 cells, EGCG was unstable, with a half-life of ∼30 minutes; EGCG dimers and other oxidative products were formed. The presence of SOD in the culture medium stabilized EGCG and increased its half-life to longer than 24 hours and some EGCG epimerized to (+)-gallocatechin-3-gallate. A mechanism of superoxide radical-mediated dimerization of EGCG and H2O2 formation is proposed. The stabilization of EGCG by SOD in the culture medium potentiated the activity of EGCG in inhibiting KYSE 150 cell growth. The results suggest that in cell culture conditions, the auto-oxidation of EGCG leads to EGFR inactivation, but the inhibition of cell growth is due to other mechanisms. It remains to be determined whether the presently observed auto-oxidation of EGCG occurs in vivo. In future studies of EGCG and other polyphenolic compounds in cell culture, SOD may be added to stabilize EGCG and to avoid possible artifacts. |
| Databáze: | OpenAIRE |
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