Physiologic and Metabolic Changes in Crepidiastrum denticulatum According to Different Energy Levels of UV-B Radiation.

Ultraviolet B (UV-B) light, as a physical elicitor, can promote the secondary metabolites biosynthesis in plants. We investigated effects of different energy levels of UV-B radiation on growth and bioactive compounds of Crepidiastrum denticulatum. Three-week-old seedlings were grown in a plant factory for 5 weeks. Plants were subjected to different levels of UV-B (0, 0.1, 0.25, 0.5, 1.0, and 1.25 W m-2), 6 h a day for 6 days. All UV-B treatments had no negative effect on the shoot dry weight; however, relatively high energy treatments (1.0 and 1.25 W m-2) inhibited the shoot fresh weight. UV-B light of 0.1, 0.25, and 0.5 W m-2 did not affect total chlorophyll and H2O2 contents; however, they increased total carotenoid content. On 4 days, 0.25 W m-2 treatment increased antioxidant capacity, total hydroxycinnamic acids (HCAs) content, and several sesquiterpenes. Treatments with 1.0 and 1.25 W m-2 increased total carotenoid, total HCAs, and H2O2 contents, and destroyed chlorophyll pigments, reducing maximum quantum yield of photosystem II and causing visible damage to leaves. Partial least squares discrimination analysis (PLS-DA) showed that secondary metabolites were distinguishably changed according to energy levels of UV-B. The potential of 0.25 W m-2 UV-B for the efficient production of bioactive compounds without growth inhibition in C. denticulatum was identified.

Association of Coffee Consumption With Total and Cause-Specific Mortality Among Nonwhite Populations.

BACKGROUND: Coffee consumption has been associated with reduced risk for death in prospective cohort studies; however, data in nonwhites are sparse. OBJECTIVE: To examine the association of coffee consumption with risk for total and cause-specific death. DESIGN: The MEC (Multiethnic Cohort), a prospective population-based cohort study established between 1993 and 1996. SETTING: Hawaii and Los Angeles, California. PARTICIPANTS: 185 855 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites aged 45 to 75 years at recruitment. MEASUREMENTS: Outcomes were total and cause-specific mortality between 1993 and 2012. Coffee intake was assessed at baseline by means of a validated food-frequency questionnaire. RESULTS: 58 397 participants died during 3 195 484 person-years of follow-up (average follow-up, 16.2 years). Compared with drinking no coffee, coffee consumption was associated with lower total mortality after adjustment for smoking and other potential confounders (1 cup per day: hazard ratio [HR], 0.88 [95% CI, 0.85 to 0.91]; 2 to 3 cups per day: HR, 0.82 [CI, 0.79 to 0.86]; ≥4 cups per day: HR, 0.82 [CI, 0.78 to 0.87]; P for trend < 0.001). Trends were similar between caffeinated and decaffeinated coffee. Significant inverse associations were observed in 4 ethnic groups; the association in Native Hawaiians did not reach statistical significance. Inverse associations were also seen in never-smokers, younger participants (<55 years), and those who had not previously reported a chronic disease. Among examined end points, inverse associations were observed for deaths due to heart disease, cancer, respiratory disease, stroke, diabetes, and kidney disease. LIMITATION: Unmeasured confounding and measurement error, although sensitivity analysis suggested that neither was likely to affect results. CONCLUSION: Higher consumption of coffee was associated with lower risk for death in African Americans, Japanese Americans, Latinos, and whites. PRIMARY FUNDING SOURCE: National Cancer Institute.

AMPK interacts with ß-catenin in the regulation of hepatocellular carcinoma cell proliferation and survival with selenium treatment.

Selenium has received much attention as an anticancer agent, although the mechanisms of action underlying its pro-apoptotic properties remain unclear. Tumors that respond well to antioxidant treatments, such as hepatocellular carcinoma (HCC), may benefit from treatment with selenium as this compound also has antioxidant properties. Furthermore, a major oncogenic driver in HCC is the nuclear transcription co-activator, ß-catenin. In the present study, we examined the mechanism by which selenium reduces survival of HCC cells, and whether this was associated with modulation of the ß-catenin pathway. Hep3B cell lines and cancer cell xenografted animals were treated with selenium, and apoptotic events or signals such as AMPK, ß-catenin and GSK3ß were determined. Further interactions among ß-catenin, glycogen synthase kinase 3ß (GSK3ß), and AMPK were explored by applying AMPK small interfering RNA (siRNA) or GSK3ß siRNA with western blotting or immunofluorescence microscopic observation. Selenium activated AMPK, which in turn suppressed ß-catenin. Selenium induced the translocation of AMPK into the nucleus and prevented the accumulation of ß-catenin therein. Upon inactivation of AMPK by AMPK siRNA, selenium no longer modulated ß-catenin, implying that AMPK is an upstream signal for ß-catenin. We found that the binding between AMPK and ß-catenin occurs in the cytosolic fraction, and therefore concluded that the cancer cell antiproliferative effects of selenium are mediated by a GSK3ß-independent AMPK/ß-catenin pathway, although AMPK-mediated GSK3ß regulation was also observed. We primarily discovered that AMPK is a crucial regulator initiating selenium-induced inhibition of ß-catenin expression. Taken together, these novel findings help to illuminate the molecular mechanisms underlying the anticancer effect of selenium and highlight the regulation of ß-catenin by selenium.

Antiproliferative effect of the methanol extract from the roots of Petasites japonicus on Hep3B hepatocellular carcinoma cells in vitro and in vivo.

Traditional medicinal plants have been used in the treatment of various diseases for centuries. A number of plant-derived compounds have been proposed as anticancer agents and are currently undergoing medical development. Petasites japonicus (PJ), also known as Butterbur, is a herb cultivated in East Asia that is used as a traditional herbal medicine. The aim of the present study was to investigate whether a methanol extract of PJ demonstrated anticancer activity against Hep3B hepatocellular carcinoma (HCC) cells. The anticancer property and underlying mechanism of the extract were evaluated by assessing the effect on cell viability, nuclear morphology and the expression of phosphorylated (p)-mTOR, p-Akt, ß-catenin and p-glycogen synthase kinase-3ß, which are markers for cancer cell proliferation and metastasis. These results were obtained by the MTT assay, fluorescence microscopy and Western blot analysis. The methanol extract of PJ was shown to decrease the cell viability in a concentration-dependent manner. In addition, the methanol extract of PJ was found to inhibit the growth of Hep3B HCC cells through inhibiting the Akt/mTOR and Wnt signaling pathways. These results suggest that the methanol extract of PJ exerts an anticancer effect on Hep3B HCC cells.

The involvement of AMPK/GSK3-beta signals in the control of metastasis and proliferation in hepato-carcinoma cells treated with anthocyanins extracted from Korea wild berry Meoru.

BACKGROUND: Activation of the Wnt pathway is known to promote tumorigenesis and tumor metastasis, and targeting Wnt pathway inhibition has emerged as an attractive approach for controlling tumor invasion and metastasis. The major pathway for inhibiting Wnt is through the degradation of ß-catenin by the GSK3-beta/CK1/Axin/APC complex. It was found that Hep3B hepato-carcinoma cells respond to anthocyanins through GSK3-beta-induced suppression of beta-catenin; however, they cannot dephosphorylate GSK3-beta without AMPK activation. METHODS: We tested the effects of anthocyanins on proliferation and apoptosis by MTT and Annexin V-PI staining in vitro. Mouse xenograft models of hepato-carcinomas were established by inoculation with Hep3B cells, and mice were injected with 50 mg/kg/ml of anthocyanins. In addition, protein levels of p-GSK3-beta, beta-catenin, p-AMPK, MMP-9, VEGF, and Ang-1 were also analyzed using western blot. RESULTS: Anthocyanins decrease phospho-GSK3-beta and beta-catenin expression in an in vivo tumor xenograft model, increase AMPK activity in this model, and inhibit cell migration and invasion, possibly by inhibiting MMP-2 (in vitro) and the panendothelial marker, CD31 (in vivo). To elucidate the role of the GSK3-beta/beta-catenin pathway in cancer control, we conditionally inactivated this pathway, using activated AMPK for inhibition. Further, we showed that AMPK siRNA treatment abrogated the ability of anthocyanins to control cell proliferation and metastatic potential, and Compound C, an AMPK inhibitor, could not restore GSK3-beta regulation, as exhibited by anthocyanins in Hep3B cells. CONCLUSION: These observations imply that the AMPK-mediated GSK3-beta/beta-catenin circuit plays crucial roles in inhibiting cancer cell proliferation and metastasis in anthocyanin-treated hepato-carcinoma cells of Meoru origin.

Multivitamin use and the risk of mortality and cancer incidence: the multiethnic cohort study.

Although multivitamin/mineral supplements are commonly used in the United States, the efficacy of these supplements in preventing chronic disease or premature death is unclear. To assess the relation of multivitamin use with mortality and cancer, the authors prospectively examined these associations among 182,099 participants enrolled in the Multiethnic Cohort Study between 1993 and 1996 in Hawaii and California. During an average 11 years of follow-up, 28,851 deaths were identified. In Cox proportional hazards models controlling for tobacco use and other potential confounders, no associations were found between multivitamin use and mortality from all causes (for users vs. nonusers: hazard ratio = 1.07, 95% confidence interval: 0.96, 1.19 for men; hazard ratio = 0.96, 95% confidence interval: 0.85, 1.09 for women), cardiovascular diseases, or cancer. The findings did not vary across subgroups by ethnicity, age, body mass index, preexisting illness, single vitamin/mineral supplement use, hormone replacement therapy use, and smoking status. There also was no evidence indicating that multivitamin use was associated with risk of cancer, overall or at major sites, such as lung, colorectum, prostate, and breast. In conclusion, there was no clear decrease or increase in mortality from all causes, cardiovascular disease, or cancer and in morbidity from overall or major cancers among multivitamin supplement users.

Suppression of mTOR via Akt-dependent and -independent mechanisms in selenium-treated colon cancer cells: involvement of AMPKalpha1.

Activation of the mammalian target of rapamycin (mTOR) pathway promotes tumorigenesis, and inhibiting the mammalian target of rapamycin complex 1 (mTORC1) has emerged as an attractive target for suppressing tumor growth. We found that selenium treatment of HT-29 colon cancer cells suppressed mTORC1 through Akt-independent and -dependent pathways. In Akt-independent mTORC1 inhibition in selenium-treated colon cancer cells, adenosine monophosphate-activated protein kinase (AMPK) alpha(1) was crucial for suppression of mTORC1 activity. In contrast, the Akt-dependent mTORC1 inhibition by selenium did not require AMPKalpha(1). The importance of the AMPKalpha(1)-mTORC1 pathway in mediating the antiproliferative action of selenium was examined in xenograft tumors, and the suppression of mTORC1 as well as Akt was concomitant with an increase in AMPKalpha(1) activity. These findings suggest that the antiproliferative effect of selenium is mediated by an Akt-independent AMPKalpha(1)/mTORC1 pathway or by the Akt/tuberous sclerosis complex 2 /mTORC1 pathway.

Nutrient intake from multivitamin/mineral supplements is similar among users from five ethnic groups: the Multiethnic Cohort Study.

A multivitamin/mineral supplement is the most widely used type of dietary supplement among American adults. Therefore, accurate assessment of intake from this supplement is crucial when studying diet and chronic diseases. From 1999 to 2001, the Multiethnic Cohort Study collected detailed information on multivitamin/mineral use among five ethnic groups: African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites. Daily nutrient intakes from multivitamin/minerals were calculated using the nutrient composition specified on the product label. For reported supplements with insufficient detail to match to a specific product, default nutrient profiles were assigned. Multivitamin/mineral use was reported by 50% of the participants (38% for Native Hawaiians to 57% for whites). Default profiles were assigned for 38% of users. The median daily nutrient intakes from multivitamin/minerals among users (n=75,865) were well above the Recommended Daily Allowance or Adequate Intake for vitamins A, B-6, B-12, and E, thiamin, riboflavin, niacin, pantothenic acid, folate, and zinc. Although nutrient intakes from multivitamin/minerals varied widely among individuals, there was no substantial difference in the median intake across ethnic groups. To accurately estimate nutrient intakes from multivitamin/minerals, detailed information on the product consumed should be collected. When detailed information is not available, the same default nutrient profiles can be used when estimating intakes for these five ethnic groups.

Calcium, vitamin D, and dairy product intake and prostate cancer risk: the Multiethnic Cohort Study.

High intakes of calcium and dairy products have been suggested to be related to prostate cancer risk. Such associations were examined in the Multiethnic Cohort Study (1993-2002) among 82,483 men who completed a detailed quantitative food frequency questionnaire. During a mean follow-up of 8 years, 4,404 total cases of prostate cancer were identified. In Cox proportional hazards models, no association was found between calcium and vitamin D intake and total, advanced, or high-grade prostate cancer risk, whether for total intake, intake from foods, or intake from supplements, among all male participants or among nonusers of supplemental calcium. No association of calcium or vitamin D intake was seen across racial/ethnic groups. In analyses of food groups, dairy product and total milk consumption were not associated with prostate cancer risk. However, low-/nonfat milk was related to an increased risk and whole milk to a decreased risk of total prostate cancer; after stratification, these effects were limited to localized or low-grade tumors. Although the findings from this study do not support an association between the intakes of calcium and vitamin D and prostate cancer risk, they do suggest that an association with milk consumption may vary by fat content, particularly for early forms of this cancer.

Calcium and vitamin D intake and risk of colorectal cancer: the Multiethnic Cohort Study.

The associations of intakes of calcium and vitamin D with colorectal cancer risk were examined in the Multiethnic Cohort Study (Hawaii and Los Angeles, California). In 1993-1996, 85,903 men and 105,108 women aged > or =45 years completed a quantitative food frequency questionnaire. A total of 2,110 incident cases of colorectal cancer (1,138 in men and 972 in women) were identified through December 31, 2001. Cox proportional hazards models were used to calculate multivariate-adjusted relative risks and 95% confidence intervals. Total calcium intake (from foods and supplements) was inversely associated with colorectal cancer risk in both men (highest quintile vs. lowest: relative risk (RR) = 0.70, 95% confidence interval (CI): 0.52, 0.93; p for trend = 0.006) and women (RR = 0.64, 95% CI: 0.50, 0.83; p for trend = 0.003). The inverse association was also seen for total vitamin D intake in men (RR = 0.72, 95% CI: 0.51, 1.00; p for trend = 0.03) but not in women. Intake of dairy products was inversely associated with colorectal cancer risk, especially among nonusers of supplemental calcium (men: RR = 0.77, 95% CI: 0.59, 1.01; women: RR = 0.66, 95% CI: 0.49, 0.89). The findings support the hypothesis of protective roles for calcium, vitamin D, and dairy products in the risk of colorectal cancer.

Multivitamin-multimineral supplements' effect on total nutrient intake.

Use of multivitamin-multimineral supplements is widespread and can contribute substantially to total nutrient intakes. In the Hawaii-Los Angeles Multiethnic Cohort (MEC), 48% of men and 56% of women without chronic diseases reported use of multivitamin supplements at least weekly over the past year. We calculated the prevalence of nutrient adequacy for 17 nutrients based on responses to a self-administered quantitative food-frequency questionnaire administered to MEC participants at baseline in 1993-1996. Although the prevalence of nutrient adequacy from food only was higher for multivitamin supplement users (n = 21,056) than for nonusers (n = 69,715), differences averaged only 2 percentage points. For multivitamin users, the prevalence of adequacy improved by an average of 8 percentage points for both men and women when intake from supplements was included. Users were also more likely to have potentially excessive intakes, particularly for iron, zinc, vitamin A, and niacin. The 26,735 MEC participants in Hawaii who answered an open-ended question about multivitamin use in 1999-2001 reported using 1246 different products. The nutrient profile of these products varied widely, and the composition of products at the 90th percentile was 10-fold greater than the composition at the median for some nutrients. We conclude that analyses of nutrient adequacy and excess for supplement users should be extended to national samples and that composition data on actual supplements used are preferable to assuming a default nutrient profile for multivitamin supplements. Multivitamin products could be better formulated to reduce the prevalence of inadequacy and also to reduce the risk of excessive intakes.

Allowing for variations in multivitamin supplement composition improves nutrient intake estimates for epidemiologic studies.

Collecting detailed data on dietary supplement use is time-consuming for study participants and investigators, and this is particularly difficult for multivitamin use because of the many different formulations available. Therefore, many studies simply ask about the frequency of multivitamin use and assign default nutrient composition values to obtain nutrient intakes. Multivitamin supplements are important contributors to total nutrient intakes, but it is not known how default values affect the accuracy of intake estimation. In this study, nutrient intakes were calculated from multivitamins consumed by 26,735 multivitamin users who provided detailed information like product name(s) and frequency of use on a mailed questionnaire. We then recalculated the intakes, using 2 different assumptions about the composition of the multivitamin supplements: 1) a single default composition for all products; and 2) four default compositions, 1 for each subtype of multivitamin, i.e., one-a-day with minerals, one-a-day without minerals, B-complex or stress multivitamins, and antioxidant combinations. A total of 1246 different brands of multivitamins were reported and nutrient composition varied widely. Spearman correlation coefficient analyses, using the 4 default nutrient profiles compared with actual nutrient intakes, were >0.5 (P < 0.001) for 12 of 15 nutrients examined. However, correlations using the single default were lower, with only 5 correlations >0.5. Our findings suggest that a questionnaire designed to assess the composition profiles for 4 types of multivitamin products substantially improves the accuracy of nutrient-intake estimates over one that uses a single default nutrient profile for all multivitamin products.