Epidemiologic studies have examined the association between fruit and vegetable (F&V) consumption and the risk of cancer. Several cancer-preventive mechanisms have been proposed, such as antioxidant properties and modulation of biotransformation enzyme activities; both may be associated with reducing DNA damage and hence the mutation rate. We investigated, in a randomized, controlled, crossover feeding trial, the effect of 10 servings/day of botanically defined F&V for 2 wk on endogenous DNA damage; resistance to γ-irradiation damage; and DNA repair capacity in lymphocytes, measured by the Comet assay. We also explored the association between the UGT1A1*28 polymorphism and serum bilirubin concentrations and DNA damage and repair measures. Healthy men (n = 11) and women (n = 17), age 20 to 40 yr, provided blood samples at the end of each feeding period. Overall, F&V did not affect DNA damage and repair measures in lymphocytes. The number of UGT1A1*28 alleles was inversely associated with sensitivity to γ-irradiation exposure and DNA repair capacity, but a biological mechanism to explain this association is unclear. A larger sample size is needed to investigate the association between bilirubin concentrations and endogenous DNA damage. With inconsistent findings in the literature, additional dietary intervention studies on the effect of F&V on DNA damage and repair are needed.
This study’s purpose was to examine the source, storage, preparation, and intake of food among Amish and non-Amish adults to understand dietary practices as a potential contributing factor to lower cancer incidence rates. Interviews were conducted with a random sample of 134 Amish and 154 non-Amish adults including questions about dietary practices and a 24-h dietary recall. Amish compared to non-Amish adults reported (1) less refrigeration in homes (85% vs. 100%, P < .01); (2) rarely/never obtaining food from restaurants and grocery stores (P < .01); (3) consuming less alcohol (P < .01); (4) consuming fewer daily servings of vegetables (males: 1.2 vs. 1.9 servings/day, P < .01; females: 1.0 vs. 2.1 servings/day, P < .01); and (5) a greater percentage of energy from saturated fat (males: 16.7% vs. 12.6%, P < .01; females: 16.3% vs. 12.0%, P < .01). Amish males reported greater amount of energy intake (2780 kcal vs. 2298 kcal, P = .03) compared to non-Amish males. Amish and non-Amish dietary patterns show some differences that may impact cancer although neither group achieves current diet and cancer prevention guidelines. Lifestyle factors, screening, and healthcare access may be contributing to the lower cancer incidence rates among the Amish and these results suggest areas of intervention to reduce the cancer burden.
Dietary glycemic load (GL), glycemic index (GI), and carbohydrate could be associated with breast cancer risk by influencing long-term blood glucose and insulin concentrations. We examined associations between GL, GI, and carbohydrate and incident breast cancer in 148,767 Women’s Heath Initiative (WHI) participants. Dietary variables were estimated from food frequency questionnaires administered at baseline. Self-reported breast cancers during follow-up were confirmed by medical records review. Cox proportional hazards regression modeled time to breast cancer within quintiles of GL, GI, and carbohydrate. There were 6,115 total breast cancers after a median follow-up of 8.0 yr. We observed no associations between GL, GI, or carbohydrate and total incident breast cancer, with hazard ratios and 95% confidence intervals for the highest vs. lowest quintiles of 1.08, 0.92–1.29 (P for trend = 0.27); 1.01, 0.91–1.12 (P = 0.74); and 0.95, 0.80–1.14 (P = 0.98), respectively. There was a trend toward significance for the positive association between GL and in situ cancers (1.40, 0.94–2.13; P = 0.07). Although there was no evidence of associations between GL, GI, or carbohydrate and total breast cancer risk in WHI participants, the suggestion of an association between GL and risk of in situ cancers requires further investigation.
The goal of this study was to determine if a multi-mineral natural product derived from red marine algae, could reduce colon polyp formation in mice on a high fat diet. C57BL/6 mice were maintained for up to 18 months either on a high-fat “Western-style” diet or on a low-fat diet (AIN 76A), with or without the multi-mineral-supplement. To summarize, colon polyps were detected in 22 of 70 mice (31%) on the high-fat diet, but in only 2 of 70 mice (3%) receiving the mineral-supplemented high-fat diet (p<0.0001). Colon polyps were detected in 16 of 70 mice (23%) in the low-fat group; not significantly different from high-fat group but significantly higher than the high-fat-supplemented group (p=0.0006). This was in spite of the fact that the calcium level in the low-fat diet was comparable to the level of calcium in the high-fat diet containing the multi-mineral-product. Supplementation of the low-fat diet reduced the incidence to 8 of 70 mice (11% incidence). Taken together, these findings demonstrate that a multi-mineral natural product can protect mice on a high-fat diet against adenomatous polyp formation in the colon. These data suggest that increased calcium alone is insufficient to explain the lower incidence of colon polyps.
Calcium; multi-mineral natural product; trace elements; lanthanoid; colon polyps; adenocarcinoma; adenoma; chemoprevention
Most epidemiological studies evaluating the association of fruit and vegetable intakes on lung cancer risk were conducted in North American and European countries. We investigated the association of intakes of fruits, vegetables, dietary vitamins A and C, and folate with lung cancer risk among 61,491 Chinese adult men who were recruited to the Shanghai Men's Health Study, a population-based, prospective cohort study. Baseline dietary intake was assessed through a validated food frequency questionnaire during in-home visits. Multivariate Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of lung cancer risk associated with dietary intakes. During a median follow-up of 5.5 years, 359 incident lung cancer cases accrued after the first year of follow-up and 68.8% of them were current smokers. Intakes of green leafy vegetables, β-carotene-rich vegetables, watermelon, vitamin A, and carotenoids were inversely associated with lung cancer risk; the corresponding HR (95% CI) comparing the highest with the lowest quartiles were 0.72 (0.53–0.98), 0.69 (0.51–0.94), 0.65 (0.47–0.90), 0.63 (0.44–0.88), and 0.64 (0.46–0.88). Intake of all fruits and vegetables combined was marginally associated with lower risk. Our study suggests that the consumption of carotenoid-rich vegetables is inversely associated with lung cancer risk.
fruits; vegetables; carotenoids; dietary intake; lung cancer; epidemiological
Diallyl disulfide (DADS), a garlic organosulfur compound (OSC), has been researched as a cancer prevention agent; however, the role of DADS in the suppression of cancer initiation in non-neoplastic cells has not been elucidated. To evaluate DADS inhibition of early carcinogenic events, MCF-10A cells were pretreated (PreTx) with DADS followed by the ubiquitous carcinogen benzo(a)pyrene (BaP), or co-treated (CoTx) with DADS and BaP for up to 24 hours. The cells were evaluated for changes in cell viability/proliferation, cell cycle, induction of peroxide formation, and DNA damage. BaP induced a statistically significant increase in cell proliferation at 6 hours, which was attenuated with DADS CoTx. PreTx with 6 and 60 μM of DADS inhibited BaP-induced G2/M arrest by 68 and 78%, respectively. DADS, regardless of concentration or method, inhibited BaP-induced extracellular aqueous peroxide formation within 24 hours. DADS attenuated BaP-induced DNA single strand breaks at all time points through both DADS Pre- and CoTx, with significant inhibition for all treatments sustained after 6 hours. DADS was effective in inhibiting BaP-induced cell proliferation, cell cycle transitions, ROS, and DNA damage in a normal cell line, and thus may inhibit environmentally induced breast cancer initiation.
Our previous studies have shown that aberrant arachidonic acid metabolism, especially the 5-lipoxygenase (5-Lox) pathway, is involved in oral carcinogenesis, and can be targeted for cancer prevention. In order to develop potent topical agents for oral cancer chemoprevention, five known 5-Lox inhibitors from dietary and synthetic sources, Zileuton, ABT-761, Licofelone, Curcumin and Garcinol, were evaluated in silico for their potential efficacy. Garcinol, a polyisoprenylated benzophenone from the fruit rind of Garcinia spp., was found to be a promising agent based on the calculation of a theoretical activity index. Computer modeling showed that garcinol well fit the active site of 5-Lox, and potentially inhibited enzyme activity through interactions between the phenolic hydroxyl groups and the non-heme catalytic iron. In a short-term study on 7,12-dimethylbenz[a]anthracene (DMBA)-treated hamster cheek pouch, topical garcinol suppressed leukotriene B4 (LTB4) biosynthesis and inhibited inflammation and cell proliferation in the oral epithelium. In a long-term carcinogenesis study, topical garcinol significantly reduced the size of visible tumors, the number of cancer lesions, cell proliferation, and LTB4 biosynthesis. These results demonstrated that topical application of a 5-Lox inhibitor, garcinol, had chemopreventive effect on DMBA-induced hamster cheek pouch carcinogenesis.
Oral cancer; Chemoprevention; Garcinol; 5-Lipoxygenase; Topical
Tea, next to water, is the most popular beverage in the world. It has been suggested that tea consumption has the cancer-preventive effects. Epidemiological studies have indicated decreased cancer occurrence in people who regularly drink green tea. Research has also discovered numerous mechanisms of action to explain the biological effects of tea. The most abundant and popular compound studied in tea research is (−)-epigallocatechin-3-gallate or (−)-EGCG, which is a powerful antioxidant and can inhibit a number of tumor cell proliferation and survival pathways. Tea polyphenols are known to inhibit metaloproteonases, various protein kinases, and proteins that regulate DNA replication and transformation. We also reported that ester bond-containing tea polyphenols, for example, (−)-EGCG, potently and specifically inhibited the tumor proteasomal activity. We further demonstrated that methylation on green tea polyphenols under physiological conditions decreased their proteasome-inhibitory activity, contributing to decreased cancer-preventive effects of tea consumption. Since (−)-EGCG is unstable under physiological conditions, we also developed the peracetate-protected or prodrug form of (−)-EGCG, Pro-EGCG (1), and showed that Pro-EGCG (1) increases the bioavailability, stability, and proteasome-inhibitory and anti-cancer activities of (−)-EGCG in human breast cancer cells and tumors, demonstrating its potential use for cancer prevention and treatment.
Oxidation of polyunsaturated fatty acids (PUFAs) releases α, β-unsaturated aldehydes that modify deoxyguanosine (dG) to form cyclic 1,N2-propanodeoxyguanosine adducts. One of the major adducts detected in vivo is acrolein-derived 1,N2-propanodeoxyguanosine (Acr-dG). We used a chemical model system to examine the effects of four antioxidants known to inhibit fatty acid oxidation on the formation of Acr-dG and 8-oxodeoxyguaonsine (8-oxodG) from the PUFA docosahexaenoic acid (DHA) under oxidative conditions. We found that epigallocatechin gallate (EGCG) and dihydrolipoic acid (DHLA) inhibit both Acr-dG and 8-oxodG formation. In contrast, ascorbic acid and α-tocopherol actually increase Acr-dG at high concentrations and do not show a concentration-dependant inhibition of 8-oxodG. We also studied their effects on blocking Acr-dG formation directly from Acr. EGCG and DHLA can both effectively block Acr-dG formation, but ascorbic acid and α-tocopherol show weak or little effect. These results highlight the complexity of antioxidant mechanisms and also reveal that EGCG and DHLA are effective at suppressing lipid-peroxidation induced Acr-dG and 8-oxodG formation as well as blocking the reaction of dG with Acr.
Effective strategies for reducing food intake are needed to reduce risk of obesity-related cancers. We investigated the effect of low and high-glycemic load (GL) diets on satiety and whether satiety varied by BMI, gender, and serum leptin. 80 normal weight (BMI=18.5-24.9 kg/m2) and overweight/obese (BMI=28.0-40.0 kg/m2) adults participated in a randomized, cross-over controlled feeding study testing low-GL vs. high-GL diets. The 28-day diets were isocaloric with identical macronutrient distributions, differing only in GL and fiber. Participants completed visual analog satiety surveys and fasting serum leptin after each 28-day period. T-tests compared mean within- and between-person satiety scores and leptin values. Participants reported 7% greater satiation on the low-GL vs. the high-GL diet (p=0.03) and fewer food cravings on the low-GL vs. the high-GL diet (p<0.001). Compared to males, females reported less hunger (p=0.05) and more satiety on the low-GL vs. the high-GL diet (p<0.01). Participants with low body fat (<25.0% for men; <32.0% for women) and BMI < 25.0 kg/m2 reported study food was tastier on the low-GL vs. the high-GL diet (p=0.04 and p=0.05, respectively). In summary, reducing GL, and/or increasing fiber, may be an effective way to lower calories consumed, improve energy balance and ultimately reduce cancer risk.
glycemic index; glycemic load; obesity; cross-over studies
The effects of diet on breast cancer are controversial and whether the effects vary with hormone receptor status has not been well investigated. This study evaluated the associations of dietary factors with risk for breast cancer overall and by hormone receptor status of tumors among Chinese women.
The Shanghai Breast Cancer Study, a large, population-based, case-control study, enrolled 3,443 cases and 3,474 controls in 1996–1998 (phase I) and 2002–2004 (phase II); 2,676 cases had ER and PR data. Dietary intake was assessed using a validated, quantitative, food frequency questionnaire (FFQ). Odds ratios (ORs) and 95% confidence intervals (95% CI) were derived from multivariate, polychotomous, unconditional logistic regression models.
Total vegetable intake was inversely related to breast cancer risk, with an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67–0.95; P trend=0.02). Reduced risk was also related to high intake of allium vegetables (P trend = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and rosaceae fruits were inversely associated with breast cancer risk (P trend = 0.003 and P trend = 0.004, respectively), although no consistent association was seen for total fruit intake. Elevated risk was observed for all types of meat and fish intake (all P trend <0.05), while intakes of eggs and milk were associated with a decreased risk of breast cancer (both P trend <0.05). There was little evidence that associations with dietary intakes varied across the four tumor subtypes or between ER+/PR+ and ER−/PR− tumors (P for heterogeneity >0.05).
Our results suggest that high intake of total vegetables, certain fruits, milk, and eggs may reduce the risk of breast cancer, while high consumption of animal-source foods may increase risk. The dietary associations did not appear to vary by ER/PR status.
Insulin resistance is thought to mediate the association between obesity and colorectal neoplasia, but no prior studies have assessed stimulated insulin sensitivity as a risk factor for colorectal neoplasia. This prospective study examined the association between insulin sensitivity measured directly using the frequently sampled intravenous glucose tolerance test (FSIGT) and later risk of colorectal adenomas. Among participants with a range of glucose tolerance levels enrolled in the Insulin Resistance Atherosclerosis Study, colonoscopies were conducted on 600 participants ages ≥ 50 yr, regardless of symptoms, about 10 yr after the first FSIGT and 5 yr after the second. Multiple logistic regression analyses were used. Within this cohort, diabetes was not associated with colorectal adenoma risk [~10 yr prior to colonoscopy adjusted odds ratio (ORadj) 1.00; 95% confidence interval (CI), 0.62–1.62 or ~5 yr prior to colonoscopy ORadj 0.96; 95% CI, 0.62–1.50]. Among non-diabetic participants, insulin sensitivity was not associated with colorectal adenoma risk at either prior study visit [lowest vs. highest insulin sensitivity, ~10 yr prior to colonoscopy ORadj 0.93; 95% CI 0.50–1.71 and ~5 yr prior to colonscopy ORadj 0.74; 95% CI, 0.38–1.46]. These results suggest that factors other than insulin sensitivity mediate the relationship between obesity and colorectal neoplasia.
Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal cancers world-wide. Despite advances in the management of HNSCC, the overall survival for patients has not improved significantly due to advanced stages at diagnosis, high recurrence rate after surgical removal, and second primary tumor development, which together underscore the importance of novel strategies for cancer prevention. Cancer chemoprevention, the use of natural or synthetic compounds to prevent, arrest, or reverse the process of carcinogenesis at its earliest stages, aims to reverse premalignancies and prevent second primary tumors. Genomics and proteomics information including initial mutation, cancer promotion, progression and susceptibility has brought molecularly targeted therapies for drug development. The development of preventive approaches using specific natural or synthetic compounds, or both, requires a depth of understanding of the cross-talk between cancer signaling pathways and networks to retain or enhance chemopreventive activity while reducing known toxic effects. Many natural dietary compounds have been identified as multiple molecular targets, effective in the prevention and treatment of cancer. This review describes recent advances in the understanding of the complex signaling networks driving cancer progression using head and neck cancer as a prototype, and of molecularly targeted natural compounds under preclinical and clinical investigation.
Head and neck squamous cell carcinoma; Chemoprevention; Molecular target; Natural compound
Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5mg azoxymethane (AOM)/kg. In Experiments 1 and 2, female A/J mice received ANC in diet. In Experiment 1, ANC dose initially dropped sharply because the ANC precursors had mostly decomposed but, later in Experiment 1 and throughout Experiment 2, ANC remained at 85 nmol/g diet. Mice were killed after 8 (AOM tests) or 17–34 (ANC tests) wk. Median numbers of aberrant crypts in the distal 2 cm of the colon for 1 and 3 AOM injections, CF1 controls, ANC (Experiment 1), ANC (Experiment 2),and untreated A/J mice were 31, 74, 12, 20, 12, and 5–6, with P < 0.01 for both ANC tests. Experiment 2 showed somewhat increased numbers of colonic mucin-depleted foci in the ANC-treated group. We conclude that hot-dog-derived ANC induced significant numbers of aberrant crypts in the mouse colon.
Aberrant Crypt Foci; chemically induced; Animals; Azoxymethane; administration & dosage; toxicity; Carcinogens; toxicity; Colonic Neoplasms; chemically induced; Feces; chemistry; Female; Food Handling; Meat Products; analysis; toxicity; Mice; Nitrosation; Nitroso Compounds; analysis; toxicity; Sodium Nitrite; administration & dosage; metabolism
Red and processed meat consumption is associated with the risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme/alcenal, heterocyclic amines or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis. The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate heme-induced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, salivary nitrite did not change the effect of hemoglobin on biochemical markers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon of rat. However, ingested sodium nitrite increased fecal nitroso-compounds level, but their fecal concentration and their nature (iron-nitrosyl) would not be associated with an increased risk of cancer. The rat model could thus be relevant to study the effect of red meat on colon carcinogenesis in spite of the lack of nitrite recycling in rat’s saliva.
Oral consumption of freeze-dried black raspberries attenuated neoplastic changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis in colorectal cancer (CRC) patients. To determine, whether plasma concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL12p70, granulocyte macrophage colony stimulating factor (GM-CSF), interferon-γ, and tumor necrosis factor-α (TNF-α) were associated with berry treatment and changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis, plasma and biopsy samples of adenocarcinoma and adjacent normal-appearing colorectal tissue were collected before and during berry treatment from 24 CRC patients who had not received prior therapy and drank a slurry of black raspberry powder (20 g in 100 ml drinking water) 3 times-a-day for 1-to-9 weeks. Plasma concentrations of GM-CSF (+0.12 ± 0.04 pg/mL; P = 0.01) and IL-8 (−1.61 ± 0.71 pg/mL; P = 0.04) changed in patients receiving berries for more than 10 days. These changes were correlated with beneficial changes in markers of proliferation (rΔGM-CSF, ΔKi67 carcinoma - normal = −0.51) and apoptosis (rΔIL-8, ΔTUNEL carcinoma - normal = −0.52) observed in colorectal tissue taken within the same week. Plasma concentrations of GM-CSF and IL-8 may serve as non-invasive indicators to monitor tissue response to berry-based interventions for CRC.
black raspberries; cytokines; biomarkers; colorectal cancer; prevention
γ-Tocopherol (γT) protects against DNA-damaging effects of nitrogen oxides, yet its physiologic regulation in vivo is unknown. Observational studies indicate inverse associations of 25[OH]-vitamin D with γT and leptin. To determine whether vitamin D3 supplementation alters levels of lipid-soluble micronutrients, serum samples (N=85 subjects) from a randomized, double-blind, placebo-controlled clinical trial of vitamin D3 (800 IU) and calcium (2 g) alone and in combination were analyzed for lipid micronutrients and specific vitamin D metabolites at baseline and after 6-months of supplementation. Serum 25[OH]-vitaminD3 levels increased 55% (P < 0.0001) and 48% (P = 0.0005), whereas 25[OH]-vitaminD2 levels were lower by 48% (P = 0.26) and 21% (P = 0.36) in the vitamin D3 and vitamin D3 plus calcium groups, respectively. At baseline, γT levels were inversely associated with 25[OH]D (r = −0.31, P = 0.004). With vitamin D3 plus calcium treatment, serum α-tocopherol decreased 14% (P = 0.04), while similar changes in γT (19% decrease, P = 0.14) were observed. No significant effects were observed for D3 supplementation on leptin or retinol levels. These results are consistent with the hypothesis that vitamin D3 +/− calcium affects serum tocopherol and 25[OH]D2 levels, however, studies utilizing larger populations are warranted.
Several nutrients identified as potentially cancer protective have been inconsistently associated with non-Hodgkin lymphoma (NHL) risk. Dietary history data, including use of vitamin supplements, were collected using a semi-quantitative food frequency questionnaire administered during in-person interviews with 4,133 participants (2052 cases, 2081 controls) in a San Francisco Bay Area population-based case-control. Data were used to determine the association of intake levels of vitamins D, A and calcium with risk of NHL and NHL subtypes. Odds ratios (OR) and 95% confidence intervals (CI) were computed as estimates of relative risk using adjusted unconditional logistic regression. Increasing vitamin D intake from food and supplements was positively associated with NHL risk in men (5th quintile: OR=1.6, 95% CI= 1.0-2.4, Ptrend=0.07) and with diffuse large B-cell lymphoma (DLBCL) in women and men (5th quintile: OR=1.6, 95% CI=1.0-2.5, Ptrend=0.02), that was largely due to the effect in men (Ptrend=0.03). These results do not support a strong role for vitamin D intake with NHL risk with the exception of a potential association for DLBCL risk in men. Our results should be interpreted conservatively until further investigation in larger pooled studies can be conducted to better assess the role of vitamin D intake in lymphomagenesis.
lymphoma, non-Hodgkin; case-control studies; vitamin D; vitamin A; calcium
Phytoestrogens, heterocyclic phenols found in plants, may benefit several health outcomes. However, epidemiologic studies of the health effects of dietary phytoestrogens have yielded mixed results, in part due to challenges inherent in estimating dietary intakes. The goal of this study was to improve the estimates of dietary phytoestrogen consumption using a modified Block Food Frequency Questionnaire (FFQ), a 137-item FFQ created for the Study of Women’s Health Across the Nation (SWAN) in 1994. To expand the database of sources from which phytonutrient intakes were computed, we conducted a comprehensive PubMed/Medline search covering January, 1994 through September, 2008. The expanded database included 4 isoflavones, coumestrol and 4 lignans. The new database estimated isoflavone content of 105 food items (76.6%) versus 14 (10.2%) in the 1994 version and computed coumestrol content of 52 food items (38.0%), compared to 1 (0.7%) in the original version. Newly added were lignans; values for 104 FFQ food items (75.9%) were calculated. In addition, we report here the phytonutrient intakes for each racial and language group in the SWAN sample and present major food sources from which the phytonutrients came. This enhanced ascertainment of phytoestrogens will permit improved studies of their health effects.
Prostate cancer is the most commonly diagnosed cancer and second most common cause of cancer deaths in American men. Its long latency, slow progression, and high incidence rate make prostate cancer ideal for targeted chemopreventative therapies. Therefore, chemoprevention studies and clinical trials are essential for reducing the burden of prostate cancer on society. Epidemiological studies suggest that tea consumption has protective effects against a variety of human cancers, including that of the prostate. Laboratory and clinical studies have demonstrated that green tea components, specifically the green tea catechin (GTC) epigallocatechin gallate, can induce apoptosis, suppress progression, and inhibit invasion and metastasis of prostate cancer. Multiple mechanisms are involved in the chemoprevention of prostate cancer with GTCs; understanding and refining models of fundamental molecular pathways by which GTCs modulate prostate carcinogenesis is essential to apply the utilization of green tea for the chemoprevention of prostate cancer in clinical settings. The objective of this article is to review and summarize the most current literature focusing on the major mechanisms of GTC chemopreventative action on prostate cancer from laboratory, in vitro, and in vivo studies, and clinical chemoprevention trials.
The purpose of this study was to assess daily aspirin and supplement use among Amish and non-Amish adults living in Ohio Appalachia to understand their potential contribution to lower cancer incidence rates among the Amish.
A cross-sectional study was conducted with random samples of 134 Amish adults and 154 non-Amish adults. Face-to-face interviews about cancer-related behaviors included questions regarding aspirin and supplement use.
Amish compared to non-Amish adults reported: 1) taking significantly (p<0.05) more supplements (mean number of daily products by Amish men (3.5±3.7) and women (5.2± 4.3) vs. non-Amish men (1.4±1.3) and women (3.0±3.2)); 2) taking significantly (p<0.05) more vitamins, minerals, fiber supplements (women only), and enzymes (women only); 3) taking significantly (p<0.01) more herbal supplements (approximately 55% and 71% of Amish men and women vs. 17% and 23% of non-Amish men and women, respectively); and 4) taking significantly (p<0.05) less aspirin on a regular basis.
Aspirin and supplement use among Amish and non-Amish adults show significant differences characteristic of their social and cultural norms. Future studies that clarify the impact of aspirin and supplement use among the Amish and their impacts upon the risk of certain cancers and other disease processes are warranted.
Supplements; Aspirin; Amish; Appalachia
Resveratrol (3, 4', 5-trihydroxystilbene), a naturally-occurring phytoalexin readily available in the diet, is reported to possess both chemopreventive and chemotherapeutic activities in several cancers. However, despite the identification of numerous molecular targets, the underlying mechanisms involved in the anticancer activities of resveratrol are not completely understood. Resveratrol is postulated to function as a potential signaling pathway modulator and as such, is demonstrated to affect a multitude of signal transduction pathways associated with tumorigenesis and/or carcinogenesis; it is likely that this collective activity, rather than just a single effect, may play an important role in the anticancer properties of resveratrol. Since transcription factors control the expression of many genes, the elucidation of molecular targets of resveratrol involved in transcriptional regulation is necessary to better understand how this dietary phytochemical affects chemopreventive and chemotherapeutic processes. As a result, investigators have increasingly searched for and examined possible targets of resveratrol. In this review, we summarize the current knowledge on molecular targets, specifically transcription factors, that contribute to the observed anticancer effects of resveratrol related to: (1) inhibition of carcinogenic activation and induction of carcinogen detoxification, (2) induction of growth arrest and apoptosis, and (3) suppression of pro-inflammatory signaling pathways related to cancer progression.
AhR; ATF3; Experimental; FOXO; Resveratrol
We previously demonstrated that 50% of (−)-epigallocatechin gallate (EGCG) was present in methylated form (4″-MeEGCG) in human prostate tissue, which is less bioactive. We therefore investigated whether quercetin, a natural inhibitor of catechol-O-methyl transferase (COMT), will inhibit EGCG methylation leading to enhanced antiproliferative activity of EGCG in prostate cancer cells. Incubation with both, quercetin and EGCG, for 2 hr increased the cellular concentrations of EGCG by 4 to 8-fold and 6 to 10-fold in androgen-independent PC-3 cells and androgen-dependent LNCaP cells, respectively. Concurrently, the percent of 4″-MeEGCG in the total EGCG was decreased from 39% to 15% in PC-3 cells and from 61% to 38% in LNCaP cells. Quercetin and EGCG in combination synergistically inhibited cell proliferation, caused cell cycle arrest and induced apoptosis in PC-3 cells. In LNCaP cells EGCG and quercetin exhibited a stronger antiproliferative activity leading to an additive effect. The synergistic effect of these two agents in PC-3 cells could be based on the fact that EGCG primarily inhibited COMT activity while quercetin reduced the amount of COMT protein. In summary, quercetin combined with EGCG in vitro demonstrated enhanced inhibition of cell proliferation by increasing the intracellular concentration of EGCG and decreasing EGCG methylation.
Catechol-O-methyl transferase; experimental; green tea polyphenol; prostate cancer; quercetin
The mechanism by which cancer mediates muscle atrophy has been delineated in the past 3 decades, and includes a prominent role of tumor-derived cytokines, such as IL-6, TNFα and IL-1. These cytokines interact with their cognate receptors on muscle to activate the downstream transcription factor NF-κB and induce sarcomere proteolysis. Experimentally, inhibiting NF-κB signaling largely prevents cancer-induced muscle wasting, indicating its prominent role in muscle atrophy. Resveratrol, a natural phytoalexin found in the skin of grapes, has recently been shown to inhibit NF-κB in cancer cells, which led us to hypothesize that it might have a protective role in cancer cachexia. Therefore, we investigated if daily oral resveratrol could protect against skeletal muscle loss and cardiac atrophy in an established mouse model. We demonstrate resveratrol inhibits skeletal muscle and cardiac atrophy induced by C26 adenocarcinoma tumors through its inhibition of NF-κB (p65) activity in the skeletal muscle and heart. These studies demonstrate for the first time the utility of oral resveratrol therapy to provide clinical benefit in cancer-induced atrophy through the inhibition of NF-κB in muscle. These findings may have application in the treatment of diseases with parallel pathophysiologies such as muscular dystrophy and heart failure.
resveratrol; cancer cachexia; skeletal muscle; cardiac; atrophy; NF-κB inhibition