RESUMEN
Despite enormous progress in modern medicine, prostate cancer (PCa) remains a major public health problem due to its high incidence and mortality. Although studies have shown in vitro antitumor effects of cucurbitacins from Cucumis sativus, the in vivo anticancer effect of the seed oil as a whole, has yet to be demonstrated. The present study evaluated the in vitro anticancer mechanisms of C. sativus (CS) seed oil and its possible chemopreventive potential on benzo(a)pyrene (BaP)-induced PCa in Wistar rat. In vitro cell growth, clone formation, cell death mechanism, cell adhesion and migration as well as expression of integrins ß-1 and ß-4 were assessed. In vivo PCa was induced in 56 male rats versus 8 normal control rats, randomized in normal (NOR) and negative (BaP) control groups which, received distilled water; the positive control group (Caso) was treated with casodex (13.5 mg/kg BW). One group received the total seed extract at the dose of 500 mg/kg BW; while the remaining three groups were treated with CS seed oil at 42.5, 85, and 170 mg/kg BW. The endpoints were: morphologically (prostate tumor weight and volume), biochemically (total protein, prostate specific antigen (PSA), oxidative stress markers such as MDA, GSH, catalase, and SOD) and histologically. As results, CS seed oil significantly and concentration-dependently reduced the DU145 prostate cancer cell growth and clone formation (optimum = 100 µg/mL). It slightly increased the number of apoptotic cells and inhibited the migration and invasion of DU145 cells, while it decreased their adhesion to immobilized collagen and fibrinogen. The expression of integrin ß-1 and ß-4 was increased in presence of 100 µg/mL CS oil. In vivo, the BaP significantly elevated the incidence of PC tumors (75%), the total protein and PSA levels, pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) and MDA levels compared to NOR. CS seeds oil significantly counteracted the effect of BaP by decreasing significantly the PC incidence (12.5%), and increasing the level of antioxidant (SOD, GSH, and catalase) and anti-inflammatory cytokine IL-10 in serum. While in BaP group PCa adenocarninoma was the most representative neoplasm, rats treated with 85 and 170 mg/kg prevented it in the light of the casodex. It is conclude that CS may provide tumor suppressive effects in vitro and in vivo which makes it an interesting candidate to support the current treatment protocol.
Asunto(s)
Cucumis sativus , Cucurbitaceae , Neoplasias de la Próstata , Humanos , Masculino , Ratas , Animales , Benzo(a)pireno/toxicidad , Catalasa , Cucumis sativus/metabolismo , Antígeno Prostático Específico/uso terapéutico , Cucurbitaceae/metabolismo , Ratas Wistar , Citocinas/metabolismo , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/prevención & control , Superóxido Dismutasa , Aceites de Plantas/farmacología , Aceites de Plantas/uso terapéuticoRESUMEN
PURPOSE: This study aimed to assess the effects of 20 wk resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance, and aerobic capacity in prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS: Sixty prostate cancer patients receiving ADT were randomly assigned to perform 20 wk of resistance exercise training with supplementation of 31 g whey protein (EX + PRO, n = 30) or placebo (EX + PLA, n = 30), consumed immediately after exercise and every night before sleep. A separate control group (CON, n = 36) only received usual care. At baseline and after 20 wk, body composition (dual-energy x-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-Second Chair Stand Test, and Stair Climb Test), aerobic capacity (cardiopulmonary exercise test), and habitual dietary intake (food diary) were assessed. Data were analyzed using a two-factor repeated-measures ANOVA. RESULTS: Over time, muscle mass and strength increased in EX + PRO and EX + PLA and decreased in CON. Total fat mass and fat percentage increased in EX + PRO and CON, but not in EX + PLA. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in EX + PLA, but it decreased in EX + PRO and CON. Habitual protein intake (without supplements) averaged >1.0 g·kg body weight -1 ·d -1 , with no differences over time or between groups. CONCLUSIONS: In prostate cancer patients, resistance exercise training counteracts the adverse effects of ADT on body composition, muscle mass, muscle strength, and aerobic capacity, with no additional benefits of protein supplementation.
Asunto(s)
Neoplasias de la Próstata , Entrenamiento de Fuerza , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/inducido químicamente , Antagonistas de Andrógenos/efectos adversos , Andrógenos/farmacología , Andrógenos/uso terapéutico , Equilibrio Postural , Estudios de Tiempo y Movimiento , Suplementos Dietéticos , Fuerza Muscular/fisiología , Composición Corporal , Músculos , Poliésteres/farmacología , Terapia por EjercicioRESUMEN
Selenomethionine (SeMet) did not prevent prostate cancer in the SELECT trial and in two hormone-driven rat models. However, we have shown that daily oral bolus administration of next-generation selenium forms, methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) at 3 mg Se/kg body weight, inhibits prostate carcinogenesis in the TRAMP and pten-deficient mouse models and In Vivo growth of human prostate cancer cells. Here, we determined whether these Se forms prevent prostate cancer in a chemically induced-androgen promoted carcinogenesis rat model in which SeMet was not preventive. WU rats were treated with methylnitrosourea, and one week later, slow-release testosterone implants when they were randomized to groups fed AIN-93M diet supplemented with 3 ppm selenium as MSeA or MSeC or control diet. Mean survival, tumor incidence in all accessory sex glands combined (dorsolateral and anterior prostate plus seminal vesicle) and the incidence of tumors confined to dorsolateral and/or anterior prostate were not statistically significantly different among the groups. Thus, MSeA and MSeC feeding was not preventive in this model. The contrast with the inhibitory effects of MSeA and MSeC in mouse models may be due to differences in carcinogenic mechanisms, selenium dosage, delivery mode, and pharmacokinetics or fundamental rat-mouse differences in selenium metabolism.
Asunto(s)
Neoplasias de la Próstata , Selenio , Andrógenos/metabolismo , Animales , Antioxidantes/metabolismo , Carcinogénesis/inducido químicamente , Carcinógenos , Dieta , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Compuestos de Organoselenio , Próstata/metabolismo , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/prevención & control , Ratas , Selenio/metabolismo , Selenio/farmacología , Selenocisteína/análogos & derivados , Selenocisteína/metabolismo , Selenocisteína/farmacología , Selenometionina/metabolismo , Selenometionina/farmacologíaRESUMEN
The ß-isomer of hexachlorocyclohexane (ß-HCH) is a globally widespread pollutant that embodies all the physicochemical characteristics of organochlorine pesticides, constituting an environmental risk factor for a wide range of noncommunicable diseases. Previous in vitro studies from our group disclosed the carcinogenic potential of ß-HCH, which contributes to neoplastic transformation by means of multifaceted intracellular mechanisms. Considering the positive evidence regarding the protective role of natural bioactive compounds against pollution-induced toxicity, micronutrients from olive and tomato endowed with the capability of modulating ß-HCH cellular targets were tested. For this purpose, the solution obtained from a patented food supplement (No. EP2851080A1), referred to as Tomato and Olive Bioactive Compounds (TOBC), was administered to the androgen-sensitive prostate cancer cells LNCaP and different biochemical and cellular assays were performed to evaluate its efficiency. TOBC shows a dose-dependent significant chemoprotection by contrasting ß-HCH-induced intracellular responses such as STAT3 and AhR activation, disruption of AR signaling, antiapoptotic and proliferative activity, and increase in ROS production and DNA damage. These experimental outcomes identified TOBC as a suitable functional food to be included in a diet regimen aimed at defending cells from ß-HCH negative effects, recommending the development of tailored enriched formulations for exposed individuals.
Asunto(s)
Fitoquímicos/farmacología , Neoplasias de la Próstata/dietoterapia , Receptores Androgénicos/genética , Factor de Transcripción STAT3/genética , Andrógenos/metabolismo , Proliferación Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Hexaclorociclohexano/toxicidad , Humanos , Solanum lycopersicum/química , Masculino , Micronutrientes/química , Micronutrientes/farmacología , Olea/química , Fitoquímicos/química , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Especies Reactivas de Oxígeno/química , Factores de Riesgo , Transducción de Señal/efectos de los fármacosRESUMEN
Bisphenol A (BPA) is a chemical agent which can exert detrimental effects on the male reproductive system, especially the prostate gland. In this study we described the efficacy of the dietary agent curcumin, alone or combined with piperine, to suppress the impact of BPA on the prostate. Adult gerbils were divided into nine experimental groups (n = 7 each group), regarding control (water and oil), exposed to BPA (50 µg/kg/day in water) or curcumin (100 mg/kg) and/or piperine (20 mg/kg). To evaluate the effects of the phytotherapic agents, the other groups received oral doses every two days, BPA plus curcumin (BCm), piperine (BP), and curcumin + piperine (BCmP). BPA promoted prostatic inflammation and morphological lesions in ventral and dorsolateral prostate lobes, associated with an increase in androgen receptor-positive cells and nuclear atypia, mainly in the ventral lobe. Curcumin and piperine helped to minimize these effects. BPA plus piperine or curcumin showed a reduction in nuclear atypical phenotype, indicating a beneficial effect of phytochemicals. Thus, these phytochemicals minimize the deleterious action of BPA in prostatic lobes, especially when administered in association. The protective action of curcumin and piperine consumption is associated with weight loss, anti-inflammatory potential, and control of prostate epithelial cell homeostasis.
Asunto(s)
Alcaloides/farmacología , Compuestos de Bencidrilo/toxicidad , Benzodioxoles/farmacología , Curcumina/farmacología , Fenoles/toxicidad , Fitoquímicos/farmacología , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Neoplasias de la Próstata , Animales , Carcinogénesis/inducido químicamente , Disruptores Endocrinos/toxicidad , Gerbillinae , Masculino , Próstata/efectos de los fármacos , Próstata/patología , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/patología , Sustancias ProtectorasRESUMEN
INTRODUCTION: Aerobic training and green tea extract can be used to reduce the risk of prostate cancer. The goal of this study was to evaluate the effects of 8-wk aerobic exercise training and administration of green tea extract on the level of nuclear factor kappa B (NF-kB), cyclooxygenase-2 (COX-2) and p53 tumor suppressor protein (p53) in prostate of rats which were stimulated by N-methyl-N-nitrosourea to induce the prostate cancer. METHODS: Sixty adult male Wistar rats were assigned into six groups including healthy control, cancer control (CCt), cancer training (CTr: 45 min·d at low to moderate intensity, five times per week, 8 wk), cancer extract (CEx: 1.34 mL of green tea extract, three times per week, 8 wk), cancer training+ cancer extract (CTr + CEx) and sham groups. Rats were sacrificed 48 h after the last intervention session, and the prostate tissue was isolated to measure the levels of NF-kB, COX-2, and p53. RESULTS: The NF-kB level in CCt group was increased significantly compared to the healthy control (P = 0.02). In the CTr group, NF-kB level was decreased significantly compared to the CCt and CEx groups (P = 0.001 and 0.05, respectively). In addition, the levels of P53 protein were reduced in CTr, CEx, and CTr + CEx groups compared to CCt group (P = 0.001, 0.02 and 0.004, respectively). No significant changes were found in the level of COX-2 between groups. CONCLUSIONS: These results suggest that a long-term exercise training combined with the intake of green tea extract may reduce levels of NF-kB and p53 in rats with prostate cancer. Given the importance of recognizing complementary therapies in this regard, future studies are warranted.
Asunto(s)
Anticarcinógenos/administración & dosificación , Condicionamiento Físico Animal , Extractos Vegetales/administración & dosificación , Neoplasias de la Próstata/prevención & control , Té , Animales , Peso Corporal , Ciclooxigenasa 2/metabolismo , Masculino , Metilnitrosourea , FN-kappa B/metabolismo , Tamaño de los Órganos , Próstata/anatomía & histología , Próstata/metabolismo , Neoplasias de la Próstata/inducido químicamente , Ratas Wistar , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
A large number of basic researches and observational studies suggested the cancer preventive activity of vitamin E, but large-scale human intervention trials have yielded disappointing results and actually showed a higher incidence of prostate cancer although the mechanisms underlying the increased risk remain largely unknown. Here we show through in vitro and in vivo studies that vitamin E produces a marked inductive effect on carcinogen-bioactivating enzymes and a pro-oxidant status promoting both DNA damage and cell transformation frequency. First, we found that vitamin E in the human prostate epithelial RWPE-1 cell line has the remarkable ability to upregulate the expression of various phase-I activating cytochrome P450 (CYP) enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), giving rise to supraphysiological levels of reactive oxygen species. Furthermore, our rat model confirmed that vitamin E in the prostate has a powerful booster effect on CYP enzymes associated with the generation of oxidative stress, thereby favoring lipid-derived electrophile spread that covalently modifies proteins. We show that vitamin E not only causes DNA damage but also promotes cell transformation frequency induced by the PAH-prototype benzo[a]pyrene. Our findings might explain why dietary supplementation with vitamin E increases the prostate cancer risk among healthy men.
Asunto(s)
Transformación Celular Neoplásica/inducido químicamente , Sistema Enzimático del Citocromo P-450/metabolismo , Suplementos Dietéticos/toxicidad , Neoplasias Experimentales/inducido químicamente , Neoplasias de la Próstata/inducido químicamente , Vitamina E/toxicidad , Células 3T3 , Animales , Benzo(a)pireno/toxicidad , Carcinógenos/toxicidad , Línea Celular , Transformación Celular Neoplásica/genética , Daño del ADN/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Micronúcleos con Defecto Cromosómico/inducido químicamente , Neoplasias Experimentales/genética , Neoplasias Experimentales/patología , Estrés Oxidativo/efectos de los fármacos , Próstata/citología , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Vitamina E/administración & dosificaciónRESUMEN
Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeatedly heated cooking oils (RCO) can generate varieties of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported as carcinogenic. RCO is one of the commonly consumed cooking and frying medium. These RCO consumption and inhalation of cooking fumes can pose a serious health hazard. Taking into account exploratory study, the present review aims to provide the consumption of RCO and its fumes cause the high incidence of genotoxic, mutagenic, tumorogenic and various cancers. The information on RCO and its fumes were collected through a library database and electronic search (ScienceDirect, PubMed, and Google Scholar). Remarkable studies demonstrated that the health adverse effects of RCO and its cooking fumes have been often attributed to their detrimental properties and ease to genotoxic, mutagenic and carcinogenic activities. RCO and its cooking fumes were found to enhance the incidence of aberrant cells, including breaks, fragments, exchanges and multiple chromosomal damages and micronuclei in a dose-dependent manner. Furthermore, the large consumption of RCO has been associated with a number of malignancies, including lung, colorectal, breast, and prostate cancers. The present review provides additional insights into the polluting features of PAHs produced various cancers via cooking activities in indoor environments.
Asunto(s)
Culinaria/métodos , Calor , Neoplasias/inducido químicamente , Aceites de Plantas/química , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Hidrocarburos Policíclicos Aromáticos/síntesis química , Animales , Neoplasias de la Mama/inducido químicamente , Carcinógenos/síntesis química , Neoplasias Colorrectales/inducido químicamente , Femenino , Humanos , Neoplasias Pulmonares/inducido químicamente , Masculino , Mutágenos , Neoplasias/epidemiología , Hidrocarburos Policíclicos Aromáticos/análisis , Neoplasias de la Próstata/inducido químicamente , Factores de RiesgoRESUMEN
BACKGROUND: This study aims to test whether Cordyceps sinensis (CS), the most expensive Asian nutrient supplement might stimulate growth of prostate cancer cells. METHODS: Impact of CS on growth of prostate cancer was determined in vivo and in vitro. RESULTS: Firstly, the serum testosterone level was significantly elevated in mice fed CS. Prostate glands were significantly enlarged (weight index 0.53 ± 0.04 mg/g vs. 0.31 ± 0.04 mg/g, P = 0.006). Furthermore, cell viability was increased twofold in the androgen-responsive prostate cancer cell line (VCaP) after CS treatment. This promoting effect disappeared after bicalutamide was added. In addition, serum prostate-specific antigen (PSA) in mice bearing VCaP xenografts was significantly elevated (0.66 ± 0.04 ng/ml vs. 0.26 ± 0.06 ng/ml, P < 0.001) after treatment with CS. Finally, VCaP tumors in mice treated with CS grew much faster (479.2 ± 78.74 mm3 vs. 283 ± 58.97 mm3, P = 0.074). However, the above promoting effects of CS were not observed in parallel studies using the PC-3 cell line which lacks AR expression. CONCLUSIONS: These results suggest that CS promotes growth of prostate cancer cells by increasing production of testosterone and stimulating the AR-dependent pathway. Additional studies are required to see whether CS is safely consumed by patients with prostate cancer.
Asunto(s)
Cordyceps , Extractos Vegetales/efectos adversos , Neoplasias de la Próstata/inducido químicamente , Testosterona/sangre , Animales , Carcinógenos/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Suplementos Dietéticos/efectos adversos , Humanos , Hormona Luteinizante/sangre , Masculino , Ratones Endogámicos BALB C , Tamaño de los Órganos/efectos de los fármacos , Próstata/efectos de los fármacos , Próstata/patología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: In this study we aimed to investigate the association between dietary phytoestrogen consumption and prostate cancer in a sample of southern Italian individuals. METHODS: A population-based case-control study on the association between prostate cancer and dietary factors was conducted from January 2015 to December 2016 in a single institution of the municipality of Catania, southern Italy (Registration number: 41/2015). A total of 118 histopathological-verified prostate cancer (PCa) cases and a total of 222 controls were collected. Dietary data was collected by using two food frequency questionnaires. RESULTS: Patients with PCa consumed significantly higher levels of phytoestrogens. Multivariate logistic regression showed that lignans (Q[quartile]4 vs. Q1, OR [odds ratio] = 4.72; p < .05) and specifically, lariciresinol (Q4 vs. Q1, OR = 4.60; p < .05), pinoresinol (Q4 vs. Q1, OR = 5.62; p < .05), matairesinol (Q4 vs. Q1, OR = 3.63; p < .05), secoisolariciresinol (Q4 vs. Q1, OR = 4.10; p < .05) were associated with increased risk of PCa. Furthermore, we found that isoflavones (Q3 vs. Q1, OR = 0.28; p < .05) and specifically, genistein (Q4 vs. Q1, OR = 0.40; p < .05) were associated with reduced risk of PCa. CONCLUSION: We found of an inverse association between dietary isoflavone intake and PCa, while a positive association was found with lignans intake.
Asunto(s)
Genisteína/administración & dosificación , Lignanos/administración & dosificación , Fitoestrógenos/administración & dosificación , Próstata/efectos de los fármacos , Neoplasias de la Próstata/prevención & control , Anciano , Estudios de Casos y Controles , Dieta , Encuestas sobre Dietas , Genisteína/efectos adversos , Humanos , Lignanos/efectos adversos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fitoestrógenos/efectos adversos , Neoplasias de la Próstata/inducido químicamente , Factores de Riesgo , Sicilia/epidemiologíaRESUMEN
Benign prostate hypertrophy (BPH) could be associated with low urinary symptoms requiring medical treatment: 5-alpha-reductase inhibitors (5-ARI) or É-blockers. Two clinical trials investigating 5-ARI use in prostate cancer (PCa) primary prevention highlighted a potential safety signal with an increased risk of high-grade PCa. Later observational studies failed to show similar results but have some limits. This paper focuses on describing the protocol of the CANARI study and its feasibility, as regards the matching process of two pseudo-anonymous databases. The study concerned patients living in the Brittany region (France) between 2010 and 2013. We designed a case-control study nested within a cohort of men treated by medical drugs licensed for symptomatic BPH between 2010 and 2011. Cases were patients with incident PCa diagnosed between 2012 and 2013 identified through French Health database (SNIIRAM). Gleason score was searched through Brittany pathology laboratories. Controls were patients without PCa diagnosis. Local pathology laboratories database was constituted in Brittany, gathering Gleason scores. No unique identification number is available in France; linkage of SNIIRAM and Brittany pathology laboratories database was made by deterministic matching. We matched 859 cases to Gleason grading (119 had Gleason score ≥8 and 740 had Gleason <8); around 22% of cases received 5-ARI and 78% α-blockers or phytotherapy. The CANARI study investigated in a population of men treated for BPH the risk of PCa with 5-ARI, according to Gleason grade thanks to SNIIRAM database enriched by local pathological results.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/efectos adversos , Laboratorios de Hospital , Patología Clínica , Hiperplasia Prostática/tratamiento farmacológico , Neoplasias de la Próstata/inducido químicamente , Estudios de Casos y Controles , Minería de Datos , Bases de Datos Factuales , Estudios de Factibilidad , Francia/epidemiología , Humanos , Incidencia , Masculino , Registro Médico Coordinado , Clasificación del Tumor , Seguridad del Paciente , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/epidemiología , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Proyectos de Investigación , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the antioxidant status and hence improve the clinical outcomes for patients with BPH and PCa. This review highlights the recent studies on prostate hyperplasia and carcinogenesis, and examines the role of OS on the molecular pathology of prostate cancer progression and treatment.
Asunto(s)
Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Dieta Alta en Grasa/efectos adversos , Progresión de la Enfermedad , Humanos , Masculino , Estrés Oxidativo , Neoplasias de la Próstata/inducido químicamenteRESUMEN
Tocopherols, the major forms of vitamin E, exist as alpha-tocopherol (α-T), ß-T, γ-T and δ-T. The cancer preventive activity of vitamin E is suggested by epidemiological studies, but recent large-scale cancer prevention trials with high dose of α-T yielded disappointing results. Our hypothesis that other forms of tocopherols have higher cancer preventive activities than α-T was tested, herein, in a novel prostate carcinogenesis model induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a dietary carcinogen, in the CYP1A-humanized (hCYP1A) mice. Treatment of hCYP1A mice with PhIP (200 mg/kg b.w., i.g.) induced high percentages of mouse prostatic intraepithelial neoplasia (mPIN), mainly in the dorsolateral glands. Supplementation with a γ-T-rich mixture of tocopherols (γ-TmT, 0.3% in diet) significantly inhibited the development of mPIN lesions and reduced PhIP-induced elevation of 8-oxo-deoxyguanosine, COX-2, nitrotyrosine, Ki-67 and p-AKT, and the loss of PTEN and Nrf2. Further studies with purified δ-T, γ-T or α-T (0.2% in diet) showed that δ-T was more effective than γ-T or α-T in preventing mPIN formations and p-AKT elevation. These results indicate that γ-TmT and δ-T could be effective preventive agents of prostate cancer.
Asunto(s)
Anticarcinógenos/farmacología , Citocromo P-450 CYP1A2/metabolismo , Dieta , Imidazoles , Neoplasia Intraepitelial Prostática/prevención & control , Neoplasias de la Próstata/prevención & control , Tocoferoles/farmacología , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Anticarcinógenos/administración & dosificación , Ciclooxigenasa 2/metabolismo , Citocromo P-450 CYP1A2/genética , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animales de Enfermedad , Humanos , Antígeno Ki-67/metabolismo , Masculino , Ratones Transgénicos , Factor 2 Relacionado con NF-E2/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosforilación , Neoplasia Intraepitelial Prostática/inducido químicamente , Neoplasia Intraepitelial Prostática/enzimología , Neoplasia Intraepitelial Prostática/genética , Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Tocoferoles/administración & dosificación , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
Animal studies have shown that dietary omega-3 polyunsaturated fatty acids (n-3) may play a role in the development of prostate cancer, but the results of epidemiologic studies have been equivocal. Associations in humans may vary depending on study design, measurement methodology of fatty acid intake, intake ranges, and stage of cancer development. To address this, we identified 36 published studies through PubMed (Medline) from 1993 through 2013 on long-chain n-3s and prostate cancer. Exposure measurements included dietary assessment and biomarker levels. Associations for total, early, and late stage prostate cancer were examined by subgroup of study design and exposure measure type and by using forest plots to illustrate the relative strength of associations within each subgroup. We also tested for potential threshold effects by considering studies that included measurement cut-points that met intake levels recommended by the American Heart Association. We found no consistent evidence supporting a role of n-3s in either the causation or prevention of prostate cancer at any stage or grade. Results did not vary appreciably by study design, exposure measurement, intake level, or stage of cancer development.
Asunto(s)
Dieta , Ácidos Grasos Omega-3/administración & dosificación , Neoplasias de la Próstata , Estudios de Casos y Controles , Estudios de Cohortes , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Humanos , MEDLINE , Masculino , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/prevención & control , Factores de Riesgo , Ácido alfa-Linolénico/administración & dosificaciónRESUMEN
OBJECTIVE: To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. PATIENTS AND METHODS: A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. RESULTS: In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). CONCLUSION: Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/efectos adversos , Hiperplasia Prostática/tratamiento farmacológico , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/mortalidad , Antagonistas Adrenérgicos alfa/efectos adversos , Anciano , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
Epidemiological surveys show that folic acid can prevent prostate cancer, but fortified folic acid may increase the risk of the malignancy. The physician data queries from the National Cancer Institute of the USA describe folate as protective against prostate cancer, whereas its synthetic analog, folic acid, is considered to increase prostate cancer risk when taken at levels easily achievable by eating fortified food or taking over-the-counter supplements. We review the current literature to examine the effects of folate and folic acid on prostate cancer, help interpret previous epidemiologic data, and provide a clarification regarding the apparently opposing roles of folate for patients with prostate cancer. A literature search was conducted in Medline to identify studies investigating the effect of nutrition and specifically folate and folic acid on prostate carcinogenesis and progression. In addition, the National Health and Nutrition Examination Survey database was analyzed for the trends in serum folate levels before and after mandatory fortification. Folate likely plays a dual role in prostate carcinogenesis. There remains some conflicting epidemiologic evidence regarding folate and prostate cancer risk. However, there is growing experimental evidence that higher circulating folate levels can contribute to prostate cancer progression. Further research is needed to clarify these complex relationships.
Asunto(s)
Ácido Fólico/sangre , Ácido Fólico/farmacología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/inducido químicamente , Suplementos Dietéticos/efectos adversos , Progresión de la Enfermedad , Ácido Fólico/análogos & derivados , Alimentos Fortificados , Humanos , Masculino , Encuestas Nutricionales , Estado NutricionalRESUMEN
Testosterone deficiency can occur in males of all ages. In adult males, it is induced by endogenous testosterone decline through aging and other modifiable factors. Recent publications suggested the importance of the magnitude of longitudinal decline of testosterone from baseline. The baseline level and the longitudinal decline have individual variability influenced by individual factors including digit ratio, CAG repeat of the androgen receptor and sirtuin activity. Regarding treatment for testosterone deficiency, testosterone replacement therapy is the gold standard for the management of testosterone-deficient patients, and it improves three domains of testosterone deficiency symptoms, such as the physical, psychological and sexual domain. Recent reports suggested the importance of modifiable factors in the testosterone decline in addition to aging. Therefore, it might be responsible for the prevention of testosterone deficiency symptoms to maintain testosterone secretion taking account of the modifiable factors. The present article reviews the literature, and introduces contemporary perspectives and management of testosterone deficiency.
Asunto(s)
Envejecimiento/sangre , Terapia de Reemplazo de Hormonas , Fitoterapia , Neoplasias de la Próstata/inducido químicamente , Testosterona/deficiencia , Testosterona/uso terapéutico , Envejecimiento/genética , Animales , Enfermedades Cardiovasculares/inducido químicamente , Ejercicio Físico/fisiología , Dedos/anatomía & histología , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Masculino , Panax , Extractos Vegetales/uso terapéutico , Receptores Androgénicos/genética , Factores de Riesgo , Sirtuina 1/metabolismo , Testosterona/sangreRESUMEN
Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 µg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (â¼5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1.
Asunto(s)
Suplementos Dietéticos , Estrógenos no Esteroides/antagonistas & inhibidores , Genisteína/uso terapéutico , Fenómenos Fisiologicos Nutricionales Maternos , Fitoestrógenos/uso terapéutico , Efectos Tardíos de la Exposición Prenatal/prevención & control , Próstata/efectos de los fármacos , Animales , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/antagonistas & inhibidores , Compuestos de Bencidrilo/toxicidad , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estrógenos no Esteroides/administración & dosificación , Estrógenos no Esteroides/toxicidad , Femenino , Masculino , Fenoles/administración & dosificación , Fenoles/antagonistas & inhibidores , Fenoles/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Próstata/metabolismo , Próstata/patología , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Hiperplasia Prostática/prevención & control , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/prevención & control , Ratas Sprague-Dawley , Receptores Androgénicos/metabolismo , Organismos Libres de Patógenos Específicos , DesteteRESUMEN
BACKGROUND: Cadmium is classified as a human lung carcinogen based on evidence from high-exposure occupational settings. Though cadmium has no physiological role, increasing evidence suggests cadmium may mimic steroid hormones. This dual ability of being carcinogenic and hormone-like makes cadmium a concern for hormone-related cancers. Causes of prostate cancer are not clear, but steroid hormones, particularly androgens and probably estrogens, may be involved. Cadmium has been positively associated with prostate cancer in occupationally exposed men. In non-occupationally exposed populations, diet and smoking are the main sources of cadmium exposure. The aim of this study was to investigate the association between dietary cadmium intake and prostate cancer risk in Danish men. METHODS: Dietary cadmium intake was estimated in the Danish Diet, Cancer and Health cohort at baseline 1993-97. The estimates were based on a 192 item semi-quantitative food frequency questionnaire and cadmium contents in all food items. Among 26,778 men we identified 1,567 prostate cancer cases from baseline through December 31, 2010 using the Danish Cancer Registry. The association between dietary cadmium intake and prostate cancer risk was analysed using Cox regression models. RESULTS: We did not find an association between dietary cadmium intake and prostate cancer risk (adjusted incidence rate ratio per 10 µg day(-1) = 0.98 (95% CI = 0.88-1.10)). The association did not differ according to aggressiveness of prostate cancer. Educational level, smoking status, BMI, zinc or iron intake did not modify the association. CONCLUSIONS: In our study, we did not find an association between dietary cadmium intake and prostate cancer risk in a cohort of Danish men.
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Cadmio/toxicidad , Carcinógenos/toxicidad , Suplementos Dietéticos/toxicidad , Neoplasias de la Próstata/epidemiología , Estudios de Cohortes , Suplementos Dietéticos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/patología , Factores de RiesgoRESUMEN
A substantial proportion of men with prostatic disease have an increased risk of bone loss. In the present study, we investigated the effects of Rubus coreanus Miquel (RCM) extracts on osteoporosis that occurs with N-methyl-N-nitrosourea (MNU)-induced prostatic hyperplasia. The rats used in this study were categorized into groups of healthy controls, rats treated with MNU, and rats treated with MNU and RCM. The rats were sacrificed after 10 weeks of RCM treatment, after which ultrasonography, serum biochemical tests, histopathological examinations, immunohistochemical analysis, and semi-quantitative reverse-transcription polymerase chain reaction analysis were performed. There were no marked differences in body weight gain and the size and weight of the prostate gland between the MNU group and the MNU and RCM group. However, treatment with RCM inhibited osteoclastic osteolysis and reduced dysplastic progress in the prostate gland, as observed by histopathological evaluation and by analyzing changes in the levels of bone regulatory factors. In addition, the group treated with MNU and RCM had higher expression levels of cannabinoid receptors-1, -2, and osteoprotegerin. These results indicate that the anti-osteoporotic effect of RCM in prostatic hyperplasia is attributable to the cannabinoid receptor-related upregulation of osteoblastogenesis and inhibition of prostatic hyperplasia. The results of the present study suggest that treatment with RCM may benefit osteoporotic patients with prostatic disease by simultaneously altering the activation of osteoblasts and osteoclasts.