Abstract
Based on recent evidence that tea consumption contributes to a decreased incidence of human carcinomas, a number of investigators have focused on the mechanisms of cancer prevention by tea extracts, especially green tea polyphenols. Epigallocatechin-3-galIate (EGCG) is a representative polyphenol that inhibits the activity of the cyclin-dependent kinases of cdk2 and cdk4. This suggests that EGCG may exert its growth-inhibitory effects through modulation of G1 regulatory proteins such as cdk2 and cdk4. The human biliary tract carcinoma cells (TGBC-2, SK-ChA-1, and NOZC-1) were treated with different doses of EGCG (0, 25, 50, 100, and 200 µM) for 48 hours in cell medium. Cell proliferation was analyzed by WST-1 colorimetric assay. For the cell-invasion analysis, the cells were incubated with 100 µM of EGCG for 2 hours. The cells were then added into a Matrigel-coated Cell Insert. After incubation at 37°C for 24 hours, the cells visible through the Matrigel were counted under the microscope. All human biliary tract cancer cells studied showed a significant suppression of cell growth by EGCG treatment in a dose-dependent manner (27.2%, 16.0%, and 10.1%, in TGBC-2, SK-ChA-1, and NOZC-1, respectively, at the dose of 200 µM). EpigaIlocatechin-3-gallate treatment also produced a significant suppression of invasive ability of the carcinoma cells (12.6%, 11.2%, 7.9%, in TGBC-2, SK-ChA-1, and NOZC-1, respectively, at a dose of 100 µM). These data indicated that EGCG might be a potent biological inhibitor of human biliary tract cancers, reducing their proliferative and invasive activities.
Résumé
Basé sur des indices récents semblant indiquer que la consommation en thé contribue à une incidence moindre de cancers chez l’homme, un certain nombre de chercheurs se sont intéressés aux mécanismes de prévention du cancer par les extraits de thé, et notamment les polyphénoles du thé vert. L’épigallocatéchine-3-gaIlate (EGCG) est un polyphénole représentatif qui inhibe l’activité de cdk2 et de cdk4. Ceci suggère que PEGCG pourrait exercer ses effets inhibiteurs sur la croissance par la modulation des protéines de régulation Gl telles que le cdk2 et le cdk4. Des cellules carcinomateuses des voies biliaires humaines (TGBC-2, SK-ChA-1, NOZC-1) ont été traitées par des doses variables d’EGCG (0, 25, 50, 100 et 200 µM) pendant 48 heures dans un milieu cellulaire. Cette prolifération cellulaire a été analysée par un essai colorimétrique WST-1. Pour l’analyse de l’invasion cellulaire, les cellules ont été incubées pendant deux heures dans 100 µM d’EGCG. Ensuite, les cellules ont été ajoutées à un appareil d’insertion cellulaire enduit de Matrigel. Après incubation à 37°C pendant 24 heures, les cellules envahies à travers le Matrigel ont été comptées visuellement sous microscope. Toutes les cellules humaines étudiées provenant d’un cancer des voies biliaires ont montré une suppression significative de la croissance cellulaire par le traitement par l’EGCG d’une manière dose-dépendante (27.2%, 16.0% et 0.1%, pour, respectivement, TGBC-2, SK-ChA-1 et NOZC-1, aux doses de 200 µM). Le traitement par l’EGCG a également produit une suppression significative de la capacité d’invasion (12.6%, 11.2%, 7.9%, pour, respectivement, TGBC-2, SK-ChA-1 et NOZC-1 à la dose de 100 µM). Ces données indiquent que l’EGCG pourrait être un inhibiteur biologique puissant du cancer des voies biliaires humaines, en réduisant beaucoup l’activité proliférative et invasive de ce cancer.
Resumen
Recientemente se ha demostrado que el consumo de té disminuye la frecuencia del cáncer en el ser humano. De ahí, que numerosos investigadores, intentado explicar el mecanismo preventivo del té, se hayan dedicado al estudio de sus extractos, sobre todo por lo que a los polifenoles del té verde se refiere. El Epigallocatectin-3 gallato (EGGG) constituye el más representativo de todos ellos inhibiendo la actividad de los cdk2 y cdk4. Estos hechos sugieren que el EGGG inhibe el crecimiento merced a la modulación de las proteínas reguladoras de la fase Gl, tales como cdk2 y cdk4. Células neoplásicas del árbol biliar humano (TGBC-2, SK-ChA-1, NOZC-1) fueron tratadas con diferentes concentraciones de EGGG (0, 25, 50, 100 y 200 µM) en un cultivo celular apropiado, durante 48 horas. La proliferación celular se estudió mediante el método colorimétrico WST-1. Para analizar la invasión celular se incubaron las células con 100 µM de EGGG durante 2 horas. Después, las células se trasladaron a un “Matrigel coated Cell Insert” y tras incubación a 37°C, durante 24 horas, las células que invadían el gel matricial (Matrigel) se contaron visualmente mediante microscopía. Todas las células neoplásicas procedentes del árbol biliar humano mostraron una supresión significativa (dosis dependiente) de su crecimiento, al ser sometidas a un tratamiento (dosis de 200 µM) con EGGG. (Para las TGBC-2 representó el 27.%, para las SK-ChA-1 el 16% y el 10.1% para las NOZC-1). El EGGG también provocó una supresión significativa (a dosis de 100 /utM) por lo que a la capacidad invasiva de dichas células se refiere y que fue del 12.6% para las células TGBC-2, del 11.2% para las SK-ChA-1 y del 7.9% para las NOZC-1. Los hallazgos muestran que posiblemente, el EGGG sea un potente inhibidor biológico del cáncer de árbol biliar, reduciendo su actividad tanto proliferativa como invasiva.
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Published Online: March 1, 2002
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Takada, M., Ku, Y., Habara, K. et al. Inhibitory effect of epigallocatechin-3-gallate on growth and invasion in human biliary tract Carcinoma cells. World J. Surg. 26, 683–686 (2002). https://doi.org/10.1007/s00268-001-0290-2
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DOI: https://doi.org/10.1007/s00268-001-0290-2