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1.
Int J Oncol ; 43(2): 394-404, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23754197

RESUMEN

Shoots of white asparagus are a popular vegetable dish, known to be rich in many bioactive phytochemicals reported to possess antioxidant, and anti-inflammatory and antitumor activities. We evaluated the anticancer mechanisms of a methanolic extract of Asparagus officinalis L. shoots (Asp) on human colon carcinoma cells (SW480) and their derived metastatic cells (SW620), and Asp chemopreventive properties were also assessed in a model of colon carcinogenesis. SW480 and SW620 cell proliferation was inhibited by 80% after exposure to Asp (80 µg/ml). We demonstrated that Asp induced cell death through the activation of TRAIL DR4/DR5 death receptors leading to the activation of caspase-8 and caspase-3 and to cell apoptosis. By specific blocking agents of DR4/DR5 receptors we were able to prevent Asp-triggered cell death confirming the key role of DR4/DR5 receptors. We found also that Asp (80 µg/ml) was able to potentiate the effects of the cytokine TRAIL on cell death even in the TRAIL-resistant metastatic SW620 cells. Colon carcinogenesis was initiated in Wistar rats by intraperitoneal injections of azoxymethane (AOM), once a week for two weeks. One week after (post-initiation) rats received daily Asp (0.01%, 14 mg/kg body weight) in drinking water. After 7 weeks of Asp-treatment the colon of rats exhibited a 50% reduction of the number of preneoplastic lesions (aberrant crypt foci). In addition Asp induced inhibition of several pro-inflammatory mediators, in association with an increased expression of host-defense mediators. In the colonic mucosa of Asp-treated rats we also confirmed the pro-apoptotic effects observed in vitro including the activation of the TRAIL death­receptor signaling pathway. Taken together, our data highlight the chemopreventive effects of Asp on colon carcinogenesis and its ability to promote normal cellular homeostasis.


Asunto(s)
Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Asparagus/química , Carcinogénesis/efectos de los fármacos , Neoplasias del Colon/prevención & control , Extractos Vegetales/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Animales , Azoximetano , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/patología , Activación Enzimática , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Metanol/química , Extractos Vegetales/química , Brotes de la Planta/química , Ratas , Ratas Wistar , Ligando Inductor de Apoptosis Relacionado con TNF/efectos de los fármacos
2.
Food Funct ; 4(5): 689-97, 2013 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-23403595

RESUMEN

Complex polyphenol-rich extracts from apples are known to inhibit the activity of the epidermal growth factor receptor (EGFR) in vitro. The aim of the present study was to identify the bioactive constituents of the apple juice extract which contribute substantially to this potentially chemopreventive effect and to address the question whether the effect is specific to the EGFR or whether other members of the ErbB-receptor family might also be affected. Apple-derived dihydrochalcones and their respective glycosides were found to decrease EGFR activity under cell-free conditions with IC50-values ranging from 0.4 ± 0.1 to 267.0 ± 50.0 µM but showed no activity on human cancer cells. The concentration of quercetin or its glycosides in the extract was too low to contribute substantially to the EGFR-inhibitory properties. In contrast, fractions derived from the apple juice extract comprising ≥86% oligomeric procyanidins (OPCs) suppressed the activity of the EGFR in cell culture with an IC50 ∼ 100 µg mL(-1). In addition, the activity of further members of the ErbB-receptor family was potently inhibited, with ErbB3 receptor activity being most potently decreased (IC50 ∼ 10 µg mL(-1)). From the apple polyphenols identified so far OPCs were found to add the highest contribution to the inhibitory effects towards members of the ErbB-receptor family. Considering the crucial role of the ErbB-receptors in carcinogenesis, these results support the hypothesis that apple-derived OPCs as well as OPC-rich apple preparations might be of interest with respect to chemoprevention.


Asunto(s)
Bebidas/análisis , Malus/química , Proantocianidinas/farmacología , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Línea Celular Tumoral , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Humanos , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/metabolismo , Concentración 50 Inhibidora , Fosforilación , Extractos Vegetales/farmacología , Polifenoles/farmacología , Transducción de Señal
3.
Int J Oncol ; 41(3): 849-54, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22735354

RESUMEN

The flavonolignan silibinin, the major biologically active compound of the milk thistle (Silybum marianum), has been shown to possess anticancer properties in a variety of epithelial cancers. The present study investigated the potential of silibinin as a chemopreventive agent in colon carcinogenesis. The rat azoxymethane (AOM)-induced colon carcinogenesis model was used because of its molecular and clinical similarities to sporadic human colorectal cancer. One week after AOM injection (post-initiation), Wistar rats received daily intragastric feeding of 300 mg silibinin/kg body weight per day until their sacrifice after 7 weeks of treatment. Silibinin-treated rats exhibited a 2-fold reduction in the number of AOM-induced hyperproliferative crypts and aberrant crypt foci in the colon compared to AOM-injected control rats receiving the vehicle. Silibinin-induced apoptosis in the colon mucosal cells was demonstrated by flow cytometry after propodium iodide staining and by colorimetric measurement of caspase-3 activity. Mechanisms involved in silibinin-induced apoptosis included the downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the pro-apoptotic protein Bax, inverting the Bcl-2/Bax ratio to <1. This modulation already takes place at the mRNA expression level as shown by real-time RT-PCR. Furthermore, silibinin treatment significantly (P<0.01) decreased the genetic expression of biomarkers of the inflammatory response such as IL1ß, TNFα and their downstream target MMP7, all of them shown to be upregulated during colon carcinogenesis. The downregulation of MMP7 protein was confirmed by western blot analysis. The present findings show the ability of silibinin to shift the disturbed balance between cell renewal and cell death in colon carcinogenesis in rats previously injected with the carcinogen AOM. Silibinin administered via intragastric feeding exhibited potent pro-apoptotic, anti-inflammatory and multi-targeted effects at the molecular level. The effective reduction of preneoplastic lesions by silibinin supports its use as a natural agent for colon cancer chemoprevention.


Asunto(s)
Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Transformación Celular Neoplásica/efectos de los fármacos , Neoplasias del Colon/prevención & control , Mucosa Intestinal/efectos de los fármacos , Silimarina/farmacología , Animales , Antioxidantes/farmacología , Azoximetano , Biomarcadores de Tumor , Caspasa 3/metabolismo , Neoplasias del Colon/inducido químicamente , Regulación hacia Abajo , Interleucina-1beta/biosíntesis , Mucosa Intestinal/patología , Masculino , Metaloproteinasa 7 de la Matriz/biosíntesis , Silybum marianum , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Silibina , Factor de Necrosis Tumoral alfa/biosíntesis
4.
Pathol Int ; 61(2): 80-7, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21255184

RESUMEN

By using the rat azoxymethane (AOM)-induced colon carcinogenesis model, which mirrors many clinical features of human colorectal cancer, we examined whether genetic changes occurring early in colonic mucosa are predictive of treatment efficacy. In the present study the administration of the chemopreventive agent lupulone over the course of 7 weeks postinitiation reduced the number of preneoplastic lesions in the colonic mucosa by 50%. At the molecular level we observed the downregulation of genes involved in the inflammatory response, including IL-1ß and TNF-α, and of matrix metalloproteinase-7 gene and protein expression. We also observed a substantial upregulation of components of the innate immune system, α-defensin-5 and lipocalin 2. Lupulone induced the expression of apoptosis-related genes and caused a reversal of the B-cell lymphoma/leukemia 2 (Bcl-2; antiapoptotic) to Bcl-2 associated X protein (Bax; proapoptotic) transcript and protein ratios (Bcl-2/Bax > 1 in AOM controls and Bcl-2/Bax < 1 in lupulone-treated AOM rats). Here, we identify several target genes that could be considered early biomarkers of colon carcinogenesis and indicative of drug efficacy.


Asunto(s)
Biomarcadores de Tumor/genética , Transformación Celular Neoplásica/efectos de los fármacos , Neoplasias del Colon/genética , Neoplasias del Colon/prevención & control , Expresión Génica/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Western Blotting , Quimioprevención , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Perfilación de la Expresión Génica , Inflamación/genética , Mucosa Intestinal/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Terpenos/farmacología
5.
Oncol Rep ; 23(2): 511-7, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20043115

RESUMEN

Despite numerous studies aimed at verifying the anti-tumour activity of aspirin on colon carcinogenesis little is known on the molecular targets involved in the anti-carcinogenic properties of this drug. We investigated the long-term administration of low dose of aspirin in a model of experimental colon carcinogenesis in rats. Adult Wistar rats received an intraperitoneal injection of azoxymethane (AOM) once a week for two weeks in order to initiate colon carcinogenesis. One week after AOM injection, rats received daily 0.01% aspirin (6 mg/kg body weight) in drinking water for 10 months. Compared to AOM control rats, aspirin treatment for 10 months caused a 50% reduction of the number of aberrant crypt foci associated with a 50% reduction of prostaglandin E2 (PGE2) concentration and suppressed by 80% tumour formation in the colon. RT-PCR quantitative analysis showed that aspirin treatment reduced significantly (P<0.01) the AOM-triggered increase in mRNA levels of soluble inflammatory mediators (TNFalpha and IL-1beta) and metalloproteinases (MMP3 and MMP7). Conversely, we detected an increased expression level of alpha-defensin-5 (Rd-5, 2 fold) and lipocalin-2 (LCN2, 4 fold), two markers of the innate immunity system. The expression of apoptosis-related genes such as death receptors and their ligands were reduced by aspirin and the Bcl-2/Bax transcript ratio droped, Bcl-2 expression being reduced to the level found in saline control rats. The present study identifies new molecular targets triggered by aspirin in the colonic mucosa and may support the use of non-toxic low dose of aspirin in long-term treatments as a prophylactic approach against colon carcinogenesis.


Asunto(s)
Aspirina/farmacología , Carcinoma/prevención & control , Transformación Celular Neoplásica/efectos de los fármacos , Neoplasias del Colon/prevención & control , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Aspirina/administración & dosificación , Azoximetano , Carcinógenos , Carcinoma/inducido químicamente , Carcinoma/genética , Carcinoma/inmunología , Transformación Celular Neoplásica/genética , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/genética , Neoplasias del Colon/inmunología , Evaluación Preclínica de Medicamentos , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/genética , Mediadores de Inflamación/metabolismo , Masculino , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/genética , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/prevención & control , Ratas , Ratas Wistar , Factores de Tiempo
6.
Carcinogenesis ; 28(7): 1575-81, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17434926

RESUMEN

The bitter acids of hops (Humulus lupulus L.) mainly consist of humulones or alpha-acids and lupulones or beta-acids. We aimed to evaluate the antiproliferative mechanisms of lupulones on a human metastatic colon carcinoma-derived cell line (SW620 cells) and to assess their chemopreventive effects in a model of colon carcinogenesis. SW620 cell growth was inhibited by 70% after a 48 h exposure to lupulones (40 microg/ml). Lupulones up-regulated the expression of Fas receptor (Fas) and Fas ligand (FasL) as well as TNF-related apoptosis inducing ligand (TRAIL)-R1 (DR4) and -R2 (DR5) receptor proteins, suggesting the involvement of Fas and TRAIL receptors-mediated pathways in lupulone-induced apoptosis. Lupulones also increased the mitochondrial membrane permeability. Colon carcinogenesis was initiated in Wistar rats by intra-peritoneal injections of azoxymethane (AOM), once a week for 2 weeks. One week after the last injection, rats received lupulones (0.001 or 0.005%) in drinking water, and AOM-control rats received the excipient. After 7 months of treatment, the colon of rats receiving 0.001 and 0.005% lupulones showed, respectively, a 30 and a 50% reduction (P < 0.05) of the number of preneoplastic lesions (aberrant crypt foci). In addition, we observed a drastic reduction (70-80%) of the total number of tumors in the colon of rats treated with lupulones when compared with the AOM control group. Lupulones induced apoptosis in SW620 colon-derived metastatic cells by activating both Fas and TRAIL death receptor signaling pathways, and antagonize at a low dose (4 mg/kg/day) colon cancer development. These observations suggest the use of lupulones for colon cancer chemoprevention trials.


Asunto(s)
Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias del Colon/prevención & control , Terpenos/farmacología , Animales , Anticarcinógenos/uso terapéutico , Azoximetano , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Modelos Animales de Enfermedad , Proteína Ligando Fas/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Membranas Mitocondriales/efectos de los fármacos , Membranas Mitocondriales/fisiología , Metástasis de la Neoplasia , Permeabilidad , Preparaciones de Plantas/química , Ratas , Ratas Wistar , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Terpenos/uso terapéutico , Receptor fas/metabolismo
7.
Thromb Res ; 119(2): 247-56, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-16507316

RESUMEN

Prevention of cardiovascular disease through nutritional supplements is growing in popularity throughout the world. Multiple epidemiologic studies found that moderate consumption of alcohol, particularly red wine, lowers mortality rates from coronary heart diseases (CHD). Chronic inflammation and atherosclerosis associated with CHD culminate in aberrant intravascular expression of tissue factor (TF), which triggers blood coagulation leading to thrombosis, a major cause for heart attack. We showed earlier that two red wine phenolics, resveratrol and quercetin, suppressed TF induction in endothelial cells. In the present study, we investigated efficacy of seven resveratrol derivatives, which were shown to be effective in regulating cancer cell growth in vitro at much lower concentrations than the parent compound resveratrol, in inhibiting TF induction in peripheral blood mononuclear cells (PBMCs). We also tested possible synergistic effects of resveratrol and quercetin with the other major red wine phenolics in suppression of lipopolysaccharide-induced TF expression in human PBMCs. We found that several resveratrol derivatives were 2- to 10-fold more efficient than resveratrol in inhibiting TF induction. Our study found no evidence for synergism among red wine polyphenolics. These data suggest that structural alterations of resveratrol can be effective in producing potent antithrombotic agents that will have therapeutic potential in the improvement of cardiovascular health and prevention of CHD. Among major red wine phenolics, quercetin appears to be the predominant suppressor of TF induction.


Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Monocitos/química , Fenol/farmacología , Estilbenos/farmacología , Tromboplastina/genética , Células Cultivadas , Suplementos Dietéticos , Sinergismo Farmacológico , Humanos , Monocitos/metabolismo , Quercetina/farmacología , Resveratrol , Estilbenos/química , Relación Estructura-Actividad , Vino
8.
J Agric Food Chem ; 54(15): 5410-5, 2006 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-16848525

RESUMEN

UV radiation is able to induce lipid peroxidation. Photooxidation-induced beta-sitosterol oxides were monitored in four vegetable oils exposed to sunlight for 10, 20, and 30 days during May 2005 (northeastern France), exposed to artificial light generated by a high-pressure Hg lamp for 21, 42, and 63 h at room temperature, and exposed to a 10 MeV electron beam at 0.93, 2.69, and 9.30 kGy at 8 degrees C. Quantification was performed by capillary gas chromatography-mass spectrometry according to the total ion current mode and using a reconstructed ion trace chromatogram with specific ion fragments. Sunlight induced the formation of higher amounts of oxides than UV light, while no significant oxidizing effect was observed with electron beam irradiation. However, data suggested that the amount of the main oxides formed was strongly dependent on the dose rate (length of exposure). Accordingly, shorter but more intense treatments had lower oxidizing effects.


Asunto(s)
Luz , Óxidos/análisis , Aceites de Plantas/química , Aceites de Plantas/efectos de la radiación , Sitoesteroles/análisis , Sitoesteroles/química , Ácidos Grasos Monoinsaturados , Cromatografía de Gases y Espectrometría de Masas , Peroxidación de Lípido/efectos de la radiación , Aceite de Oliva , Fotoquímica , Aceite de Brassica napus , Aceite de Soja/química , Aceite de Girasol , Luz Solar , Rayos Ultravioleta
9.
J Agric Food Chem ; 54(4): 1196-202, 2006 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-16478236

RESUMEN

A method for the separation, isolation, and identification of phytosterols was developed. A commercial phytosterols mixture, Generol 95S, was fractionated first by adsorption silica gel column chromatography and then separated by means of a semipreparative reverse phase high-performance liquid chromatography fitted with a Polaris C8-A column (250 mm x 10 mm i.d., 5 microm) using isocratic acetonitrile:2-propanol:water (2:1:1, v/v/v) as the mobile phase. Milligram scales of six individual phytosterols, including citrostadienol, campesterol, beta-sitosterol, Delta7-avenasterol, Delta7-campesterol, and Delta7-sitosterol, were obtained. Purities of these isolated sterols were 85-98%. Relative response factors (RRF) of these phytosterols were calculated against cholestanol as an authentic commercial standard. These RRF values were used to quantify by gas chromatography-mass spectrometry (GC-MS) the phytosterols content in a reference material, oils, and chocolates.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cromatografía/métodos , Análisis de los Alimentos/métodos , Fitosteroles/aislamiento & purificación , Adsorción , Cacao/química , Cromatografía en Capa Delgada , Cromatografía de Gases y Espectrometría de Masas , Fitosteroles/análisis , Aceites de Plantas/química
10.
Steroids ; 70(13): 896-906, 2005 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-16038955

RESUMEN

As vegetable oils and phytosterol-enriched spreads are marketed for frying food or cooking purposes, temperature is one of the most important factors leading to the formation of phytosterol oxides in food matrix. A methodology based on saponification, organic solvent extraction, solid-phase extraction (SPE), followed by mass spectrometric identification and quantitation of beta-sitosterol oxides using capillary gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) mode was developed and characterized. Relative response factors of six beta-sitosterol oxides, including 7alpha-hydroxy, 7beta-hydroxy, 5,6alpha-epoxy, 5,6beta-epoxy, 7-keto, and 5alpha,6beta-dihydroxysitosterol, were calculated against authentic standards of 19-hydroxycholesterol or cholestanol. Linear calibration data, limit of detection, and sample recoveries during analytical process. Recoveries of these oxidation compounds in spiked samples ranged from 88 to 115%, while relative standard derivation (R.S.D.) values were below 10% in most cases. The analytical method was applied to quantify beta-sitosterol oxides formed in thermal-oxidized vegetable oils which were heated at different temperatures and for varying time periods. Sitosterol oxidation is strikingly higher in sunflower oil relative to olive oil under all conditions of temperature and heating time.


Asunto(s)
Óxidos/análisis , Aceites de Plantas/química , Sitoesteroles/análisis , Cromatografía de Gases y Espectrometría de Masas , Calor , Aceite de Oliva , Fitosteroles/análisis , Aceite de Girasol
11.
Cancer Lett ; 215(1): 53-9, 2004 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-15374632

RESUMEN

We investigated on colon cancer cells the effect of geraniol on thymidylate synthase and thymidine kinase expression, two enzymes related to 5-fluorouracil cytotoxicity. The anti-tumoral efficacy of geraniol and 5-fluorouracil were also evaluated on TC-118 human tumors transplanted in Swiss nu/nu mice. Geraniol (150 microM) but not 5-fluorouracil caused a 2-fold reduction of thymidylate synthase and thymidine kinase expression in cancer cells. In nude mice, the combined administration of 5-fluorouracil (20 mg/kg) and geraniol (150 mg/kg) caused a 53% reduction of the tumor volume, whereas a 26% reduction was obtained with geraniol alone, 5-fluorouracil alone showed no effect.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , ADN/metabolismo , Fluorouracilo/uso terapéutico , Aceites Volátiles , Terpenos/administración & dosificación , Monoterpenos Acíclicos , Animales , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Quimioterapia Combinada , Femenino , Humanos , Ratones , Ratones Desnudos , Aceites de Plantas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Timidina Quinasa/genética , Timidina Quinasa/metabolismo , Timidilato Sintasa/genética , Timidilato Sintasa/metabolismo , Trasplante Heterólogo , Células Tumorales Cultivadas
12.
Int J Cancer ; 107(2): 189-96, 2003 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-12949793

RESUMEN

Resveratrol (3,5,4'-trihydroxystilbene) a natural polyphenol present in medicinal plants, grapes and wines, has potent chemopreventive properties on intestinal carcinogenesis. A methylated derivative (Z-3,5,4'-trimethoxystilbene: R3) was synthesized. R3 at 0.3 microM exerted a 80% growth inhibition of human colon cancer Caco-2 cells and arrested growth completely at 0.4 microM (R3 was 100-fold more active than resveratrol). The cis conformation of R3 was also 100-fold more potent than the trans isomer. R3 (0.3 microM) caused cell cycle arrest at the G2/M phase transition. The drug inhibited tubulin polymerization in a dose-dependent manner (IC50=4 microM), and it reduced also by 2-fold ornithine decarboxylase and s-adenosylmethionine decarboxylase activities. This caused the depletion of the polyamines, putrescine and spermidine, which are growth factors for cancer cells. R3 inhibited partially colchicine binding to its binding site on tubulin, indicating that R3 either partially overlaps with colchicine binding or that R3 binds to a specific site of tubulin that is not identical with the colchicine binding site modifying colchicine binding by allosteric influences. The resveratrol derivative (Z)-3,5,4'-trimethoxystilbene (R3) is an interesting anti-mitotic drug that exerts cytotoxic effects by depleting the intracellular pool of polyamines and by altering microtubule polymerization. Such a drug may be useful for the treatment of neoplastic diseases.


Asunto(s)
Adenocarcinoma/patología , Antineoplásicos Fitogénicos/farmacología , Neoplasias del Colon/patología , Mitosis/efectos de los fármacos , Estilbenos/farmacología , Moduladores de Tubulina , Adenocarcinoma/metabolismo , Apoptosis/efectos de los fármacos , Sitios de Unión , Células CACO-2/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Colchicina/metabolismo , Neoplasias del Colon/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Supresores de la Gota/metabolismo , Humanos , Microtúbulos/metabolismo , Ornitina Descarboxilasa/metabolismo , Inhibidores de la Ornitina Descarboxilasa , Poliaminas/metabolismo , Polímeros , Resveratrol , Tubulina (Proteína)/metabolismo , Vinblastina/metabolismo
13.
Cancer Lett ; 175(2): 147-55, 2002 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-11741742

RESUMEN

The effects of cocoa powder and extracts with different amounts of flavanols and related procyanidin oligomers were investigated on the growth of Caco-2 cells. Treatment of the cells with 50 microg/ml of procyanidin-enriched (PE) extracts caused a 70% growth inhibition with a blockade of the cell cycle at the G2/M phase. PE extracts caused a significant decrease of ornithine decarboxylase and S-adenosylmethionine decarboxylase activities, two key enzymes of polyamine biosynthesis. This led to a decrease in the intracellular pool of the polyamines. These observations indicate that polyamine metabolism might be an important target in the anti-proliferative effects of cocoa polyphenols.


Asunto(s)
Antioxidantes/farmacología , Biflavonoides , Cacao/química , Catequina/farmacología , División Celular/efectos de los fármacos , Flavonoides/farmacología , Extractos Vegetales/farmacología , Poliaminas/metabolismo , Proantocianidinas , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon , Humanos , Cinética , Fitoterapia , Células Tumorales Cultivadas
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