RESUMEN
Green tea, mainly through its constituents epigallocatechin gallate, epigallocatechin, epicatechin gallate and epicatechin, has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer, although less is known about colorectal cancer. Quercetin, the major flavonoid present in vegetables and fruit, exerts potential anticarcinogenic effects in animal models and cell cultures, but less is known about quercetin glucosides. The objectives of this study were to investigate (i) the antioxidant activity of the phenolic compounds epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside; (ii) the cytotoxicity of different concentrations of epicatechin, epigallocatechin gallate, and gallic acid; (iii) the cellular uptake of epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside and (iv) their effect on the cell cycle. Human colon adenocarcinoma cells were used as experimental model. The results of this study indicate that all dietary flavonoids studied (epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside) show a significant antioxidant effect in a chemical model system, but only epigallocatechin gallate or gallic acid are able to interfere with the cell cycle in Caco2 cell lines. These data suggest that the antioxidant activity of flavonoids is not related to the inhibition of cellular growth. From a structural point of view, the galloyl moiety appears to be required for both the antioxidant and the antiproliferative effects.
Asunto(s)
Adenocarcinoma/patología , Anticarcinógenos/metabolismo , Antioxidantes/metabolismo , Neoplasias del Colon/patología , Flavonoides/metabolismo , Quercetina/análogos & derivados , Anticarcinógenos/química , Anticarcinógenos/farmacología , Anticarcinógenos/toxicidad , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/toxicidad , Catequina/análogos & derivados , Catequina/química , Catequina/metabolismo , Catequina/farmacología , Catequina/toxicidad , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Flavonoides/química , Flavonoides/farmacología , Flavonoides/toxicidad , Ácido Gálico/química , Ácido Gálico/metabolismo , Ácido Gálico/farmacología , Ácido Gálico/toxicidad , Humanos , Peróxido de Hidrógeno/metabolismo , Estructura Molecular , Quercetina/química , Quercetina/metabolismo , Quercetina/farmacología , Quercetina/toxicidad , Relación Estructura-Actividad , Té/química , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismoRESUMEN
OBJECTIVES: (1) To compare tissue and plasma carotenoids status of healthy subjects and subjects with pre-cancer and cancer lesions; (2) to evaluate the effect of beta-carotene supplementation on the concentrations of other carotenoids in tissue (luteine + zeaxanthin, cryptoxanthin, lycopene, alpha-carotene) and in plasma and also retinol and alpha-tocopherol levels. DESIGN: Eighteen subjects were divided into three groups on the basis of colonoscopy and histological analytical findings: four healthy subjects (control group A); seven subjects affected by adenomatous polyps (group B with pre-cancer lesions); seven subjects suffering from colonic cancer (group C). Blood and colonic biopsy samples were taken (of colon and rectal mucosa) before and after beta-carotene supplementation in all subjects. Groups A and B received a daily dose of beta-carotene (30 mg/die) for 43 d. Group C's supplementation was terminated at the time which was performed, usually within 15 d. The tissue and plasma concentration of carotenoids, retinol and alpha-tocopherol were determined by high-performance liquid chromatography. RESULTS: The tissue concentrations of each carotenoid were similar in all the intestinal sites examined as regards groups A and B, although there was a high degree of intra individual variability within each group. Only beta-carotene made significant increases (P < 0.001) after supplementation. The subjects with cancer show tissue levels for each carotenoid lower than those of healthy subjects or subjects with polypous. The plasma levels of alpha-tocopherol did not change after supplementation while significant increases were noted of retinol, alpha-carotene (P < 0.01) and of beta-carotene (P < 0.001). CONCLUSIONS: The patients with colonic cancer seemed to undergo a significant reduction in their antioxidant reserves with respect to the normal subjects and or polyps. We can confirm that oral B-carotene supplementation induces also an increase in plasma alpha-carotene in all groups.
Asunto(s)
Carotenoides/sangre , Neoplasias del Colon/metabolismo , Mucosa Intestinal/metabolismo , Vitamina A/sangre , Vitamina E/sangre , beta Caroteno/administración & dosificación , Poliposis Adenomatosa del Colon/sangre , Poliposis Adenomatosa del Colon/metabolismo , Adulto , Anciano , Carotenoides/metabolismo , Neoplasias del Colon/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/sangre , Lesiones Precancerosas/metabolismo , beta Caroteno/sangre , beta Caroteno/metabolismoRESUMEN
We developed a method to measure plasma levels of selected polyphenols before and after ingestion of green tea. Blood samples were obtained from four healthy women before and 30 and 50 min after the ingestion of 300 ml of green tea infusion. A 1-ml volume of plasma was hydrolysed with 0.5 M HCl-methanol (1:1, v/v) for 30 min at room temperature, extracted with ethyl acetate and separated by reversed-phase chromatography. Polyphenols were identified on the basis of their retention times and by spectrum analysis. Green tea caffeine has the same retention times as caffeic acid. Consumption of green tea produces a notable increase in the plasma levels of caffeine plus caffeic acid and the appearance of measurable levels of epigallocatechingallate. In conclusion, the method was found to have the requisite features of specificity and sensitivity for monitoring plasma levels of selected tea polyphenols.