Probiotics prevent the development of 1,2-dimethylhydrazine (DMH)-induced colonic tumorigenesis through suppressed colonic mucosa cellular proliferation and increased stimulation of macrophages

Probiotics modulate immunity and inhibit colon carcinogenesis in experimental models, but these effects largely depend on the bacterial strain, and the precise mechanisms are not well understood. Therefore, we studied the effect of Bifidobacterium longum and/or Lactobacillus gasseri on the development of 1,2-dimethylhydrazine (DMH)-induced colonic precancerous lesions and tumors in mice while delineating the possible mechanisms involved. The results suggest that dietary consumption of probiotics (B. longum and L. gasseri) resulted in a significant inhibition of DMH-induced aberrant crypt foci (ACF) formation in male ICR mice. Long-term (24 weeks) dietary consumption of probiotics resulted in a reduction of colon tumor multiplicity and the size of the tumors. Administration of B. longum and L. gasseri suppressed the rate of colonic mucosa cellular proliferation in a manner correlating with the inhibition of tumor induction by DMH. In addition, the phagocytic activity of peritoneal macrophages was significantly increased in the DMH-treated mice that were fed various doses of B. longum, but not with L. gasseri or combined probiotics (B. longum + L. gasseri). We also found that L. gasseri significantly increased the proliferation of RAW264.7 macrophage cells through an increase in S phase DNA synthesis, which was related to the up-regulation of proliferating cell nuclear antigen (PCNA) and cyclin A. Taken together, these results demonstrate the in vivo chemopreventive efficacy and the immune stimulating mechanisms of dietary probiotics against DMH-induced colonic tumorigenesis.     

Peracetylated (-)-epigallocatechin-3-gallate (AcEGCG) potently suppresses dextran sulfate sodium-induced colitis and colon tumorigenesis in mice

Previous studies reported that peracetylated (-)-epigallocatechin-3-gallate (AcEGCG) has antiproliferative and anti-inflammatory activities. Here, we evaluated the chemopreventive effects and underlying molecular mechanisms of dietary administration of AcEGCG and EGCG in dextran sulfate sodium (DSS)-induced colitis in mice. The mice were fed a diet supplemented with either AcEGCG or EGCG prior to DSS induction. Our results indicated that AcEGCG administration was more effective than EGCG in preventing the shortening of colon length and the formation of aberrant crypt foci (ACF) and lymphoid nodules (LN) in mouse colon stimulated by DSS. Our study observes that AcEGCG treatment inhibited histone 3 lysine 9 (H3K9) acetylation but did not affect histone acetyltransferase (HAT) activity and acetyl- CREB-binding protein (CBP)/p300 levels. In addition, pretreatment with AcEGCG decreased the proinflammatory mediator levels by down-regulating of PI3K/Akt/NFκB phosphorylation and p65 acetylation. We also found that treatment with AcEGCG increased heme oxygenase-1(HO-1) expression via activation of extracellular signal-regulated protein kinase (ERK)1/2 signaling and acetylation of NF-E2-related factor 2 (Nrf2), thereby abating DSS-induced colitis. Moreover, dietary feeding with AcEGCG markedly reduced colitis-driven colon cancer in mice. Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary AcEGCG against inflammatory bowel disease (IBD) and potentially colon cancer associated with colitis. These findings provide insight into the biological actions of AcEGCG and might establish a molecular basis for the development of new cancer chemopreventive agents.     

Cloudy apple juice is more effective than apple polyphenols and an apple juice derived cloud fraction in a rat model of colon carcinogenesis

As recently shown, a cloudy apple juice (CloA) was effective to modulate colon cancer associated parameters in rats treated with 1,2-dimethylhydrazine (DMH). To identify the bioactive substance classes in CloA, we fractionated CloA to yield a total polyphenol (PF) and a cloud (CF) fraction consisting of proteins, fatty acids, polyphenols, and cell wall polysaccharides. Rats received water (control (Cont)) or CloA, PF, and CF separate or combined (PF-CF) ad libitum for 7 weeks starting one week before the first DMH-injection. As determined by comet assay, the DMH-induced genotoxicity in colonocytes of controls (Cont/DMH: 7.7 +/- 0.5%) was significantly reduced by CloA (3.3 +/- 0.3%) but not by any of the fractions. The crypt cell proliferation induced by DMH (Cont/NaCl: 7.5 +/- 0.6%; Cont/DMH: 14.9 +/- 0.8%) was significantly decreased by CloA (9.4 +/- 0.4%), PF (12.4 +/- 0.7%), CF (11.6 +/- 0.4%), and PF-CF (12.4 +/- 0.6%). Although not statistically significant, CloA tended to reduce the number of large aberrant crypt foci (ACF) (Cont/DMH: 19.0 +/- 3.7; CloA/DMH: 12.3 +/- 1.9), while none of the fractions affected ACFs. Neither CloA nor the fractions changed mRNAs of colonic cyclooxygenases (COX-1, COX-2), glutathione-associated enzymes (GST-M2, gamma-GCS, GST-P), the splenocyte CD4/CD8 ratio, natural killer cell activity, and plasma antioxidant status. These results demonstrate that CloA had a higher cancer-preventive potential than the fractions and further, besides PF, identified CF as an additional bioactive fraction of CloA.     

Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway

Inflammatory bowel diseases have been a risk factor of colorectal cancer (CRC). The reactive oxygen species (ROS) generated by inflammatory cells create oxidative stress and contribute to neoplastic transformation, proliferation, and even metastasis. Previously, resveratrol (RS) and pterostilbene (PS) had been reported to prevent chemical-induced colon carcinogenesis by anti-inflammatory and pro-apoptotic properties. In this study, we investigated whether RS and PS could prevent the azoxymethane (AOM)-induced colon tumorigenesis via antioxidant action and to explore possible molecular mechanisms. Male BALB/c mice were injected with AOM (5 mg/kg of body weight) with or without RS or PS, and at the end of the protocol, all of the mice were euthanized and colons were analyzed. Administrations of PS can be more effective than RS in reducing AOM-induced formation of aberrant crypt foci (ACF), lymphoid nodules (LNs), and tumors. We also find that PS is functioning more effectively than RS to reduce nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation of protein kinase C-β2 (PKC-β2) and decreasing downstream target gene expression, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and aldose reductase (AR) in mouse colon stimulated by AOM. Moreover, administration of RS and PS for 6 weeks significantly enhanced expression of antioxidant enzymes, such as heme oxygenase-1 (HO-1) and glutathione reductase (GR), via activation of NF-E2-related factor 2 (Nrf2) signaling. When the above findings are taken together, they suggest that both stilbenes block cellular inflammation and oxidative stress through induction of HO-1 and GR, thereby preventing AOM-induced colon carcinogenesis. In comparison, PS was a more potent chemopreventive agent than RS for the prevention of colon cancer. This is also the first study to demonstrate that PS is a Nrf2 inducer and AR inhibitor in the AOM-treated colon carcinogenesis model.     

Cytotoxic and antitumor activity of momilactone B from rice hulls

The cytotoxic and antitumor activity of methanolic extract of rice hulls (MERH) were evaluated by the MTT-dye reduction assay against human colon cancer cells and the colonic aberrant crypt foci (ACF) assay in 1,2-dimethylhydrazine (DMH)-injected F344 male rats, respectively. MERH was found to be highly cytotoxic, with IC50 values of 0.5 microg/mL in vitro. Forty weeks of MERH supplementation (50 mg/kg of body weight/day) reduced colonic pre-neoplastic ACF formation by 35% (p < 0.01). An active compound, momilactone B, was isolated from MERH by silica gel chromatography, Sephadex LH-20 chromatography, and HPLC. The cytotoxic activity of momilactone B was evaluated by the MTT-dye reduction, lactate dehydrogenase (LDH), and colony-forming ability assays in human colon cancer HT-29 and SW620 cells. The results indicated that momilactone B from rice hulls might be a new candidate for chemotherapeutic agent against human colon cancer.     

Cancer chemopreventive effects of lycopene: suppression of MMP-7 expression and cell invasion in human colon cancer cells

Clinical studies indicate that high blood levels of leptin or matrix metalloproteinase-7 (MMP-7; matrilysin) proteins are associated with tumor progression of human colorectal cancer (CRC). Leptin could play an important role in cell migration and invasion of cancer cells. Our previous study indicated that lycopene could inhibit the proliferation of human colon cancer cells in vitro. However, the inhibitory effects of lycopene on the progression of human colon cancer cells have not been demonstrated yet. In this study, we investigated the inhibitory effects of lycopene on tumor progression including cell invasion and MMP-7 expression in leptin-stimulated human colon cancer cells in vitro. Our results demonstrated that lycopene significantly inhibited leptin-mediated cell invasion and MMP-7 expression in human colon cancer HT-29 cells. Lycopene could augment the expression and stability of E-cadherin proteins. Our results showed that MAPK/ERK and PI3K/Akt signaling pathways played important roles in leptin-mediated MMP-7 expression and cell invasion. Lycopene could effectively inhibit the phosphorylation of Akt, glycogen synthase kinase-3β (GSK-3β) and ERK 1/2 proteins. The molecular mechanisms of lycopene were in part through decreases in nuclear levels of AP-1 and β-catenin proteins. These novel findings suggested that lycopene could act as a chemopreventive agent to suppress MMP-7 expression and leptin-mediated cell invasion in human colon cancer HT-29 cells.     

Resveratrol upregulates nrf2 expression to attenuate methylglyoxal-induced insulin resistance in hep g2 cells

Oxidative stress can result in insulin resistance, a primary cause of type-2 diabetes. Methylglyoxal (MG), a highly reactive dicarbonyl metabolite generated during glucose metabolism, has also been confirmed to cause pancreatic injury and induce inflammation, thereby resulting in insulin resistance. Recently, resveratrol has been reported to exert antioxidant properties, protecting cells from the generation of reactive oxygen species (ROS). The aim of this study was to evaluate resveratrol activation of nuclear factor erythroid 2-related factor 2 (Nrf2) to attenuate MG-induced insulin resistance in Hep G2 cells. Therefore, the molecular signaling events affecting resveratrol-mediated heme oxygenase-1 (HO-1) and glyoxalase expression levels were further investigated in this study. Our findings indicated that resveratrol activated the extracellular signal-regulated kinase (ERK) pathway but not the p38 or c-Jun N-terminal kinase (JNK) pathways, subsequently leading to Nrf2 nuclear translocation and elevation of HO-1 and glyoxalase expression levels. Moreover, resveratrol significantly elevated glucose uptake and protected against MG-induced insulin resistance in Hep G2 cells. In contrast, depletion of Nrf2 by small interfering RNA (si-RNA) resulted in the abrogation of HO-1 and glyoxalase expression in the MG-treated resveratrol group in Hep G2 cells. Administration of an appropriate chemopreventive agent, such as resveratrol, may be an alternative strategy for protecting against MG-induced diabetes.     

Inhibitory effects of feeding with carrots or (-)-falcarinol on development of azoxymethane-induced preneoplastic lesions in the rat colon

The effects of intake of dietary amounts of carrot or corresponding amounts of (-)-(3R)-falcarinol from carrots on development of azoxymethane (AOM)-induced colon preneoplastic lesions were examined in male BDIX rats. Three groups of eight AOM-treated rats were fed the standard rat feed Altromin supplemented with either 10% (w/w) freeze-dried carrots with a natural content of 35 mug falcarinol/g, 10% maize starch to which was added 35 mug falcarinol/g purified from carrots, or 10% maize starch (control). After 18 weeks, the animals were euthanized and the colon was examined for tumors and aberrant crypt foci (ACF), which were classified into four size classes. Although the number of small ACF was unaffected by the feeding treatments, the numbers of lesions as a function of increasing size class decreased significantly in the rats that received one of the two experimental treatments, as compared with the control treatment. This indicates that the dietary treatments with carrot and falcarinol delayed or retarded the development of large ACF and tumors. The present study provides a new perspective on the known epidemiological associations between high intake of carrots and reduced incidence of cancers.     

Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in humans: identification of biomarkers and individual variability

Ellagitannins (ETs) are dietary polyphenols, containing ellagic acid (EA) subunits, with antioxidant and cancer chemopreventive activities that might contribute to health benefits in humans. However, little is known about their metabolic fate. We investigate here the metabolism of different dietary ETs and EA derivatives in humans. Forty healthy volunteers were distributed in four groups. Each group consumed, in a single dose, a different ET-containing foodstuff, i.e., strawberries (250 g), red raspberries (225 g), walnuts (35 g), and oak-aged red wine (300 mL). After the intake, five urine fractions (F) were collected at 8 (F1), 16 (F2), 32 (F3), 40 (F4), and 56 (F5) h. Neither ETs nor EA were detected in urine after LC-MS/MS analysis. However, the microbial metabolite 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one (urolithin B) conjugated with glucuronic acid was detected along the fractions F3-F5 in all of the subjects, independently of the consumed foodstuff. The mean percentage of metabolite excretion ranged from 2.8 (strawberries) to 16.6% (walnuts) regarding the ingested ETs. Considerable interindividual differences were noted, identifying "high and low metabolite excreters" in each group, which supported the involvement of the colonic microflora in ET metabolism. These results indicate that urolithin B (a previously described antiangiogenic and hyaluronidase inhibitor compound) is a biomarker of human exposure to dietary ETs and may be useful in intervention studies with ET-containing products. The antioxidant and anticarcinogenic effects of dietary ETs and EA should be considered in the gastrointestinal tract whereas the study of potential systemic activities should be focused on the bioavailable urolithin B derivatives.     

Neuroprotective effects of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), in ischemic stroke of rats

Xanthohumol is the principal prenylated flavonoid in hops (Humulus lupulus L.), an ingredient of beer. Xanthohumol was found to be a potent chemopreventive agent; however, no data are available concerning its neuroprotective effects. In the present study, the neuroprotective activity and mechanisms of xanthohumol in rats with middle cerebral artery occlusion (MCAO)-induced cerebral ischemia were examined. Treatment with xanthohumol (0.2 and 0.4 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia and improved neurobehavioral deficits in cerebral ischemic rats. Xanthohumol treatment produced a marked reduction in infarct size compared to that in control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor (HIF)-1α, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions in ischemic regions. These expressions were obviously inhibited by treatment with xanthohumol. In addition, xanthohumol (3-70 μM) concentration-dependently inhibited platelet aggregation stimulated by collagen (1 μg/mL) in human platelet-rich plasma. An electron spin resonance (ESR) method was used to examine the scavenging activity of xanthohumol on free radicals which had formed. Xanthohumol (1.5 and 3 μM) markedly reduced the ESR signal intensity of hydroxyl radical (OH?) formation in the H?O?/NaOH/DMSO system. In conclusion, this study demonstrates for the first time that in addition to its originally being considered an agent preventing tumor growth, xanthohumol possesses potent neuroprotective activity. This activity is mediated, at least in part, by inhibition of inflammatory responses (i.e., HIF-1α, iNOS expression, and free radical formation), apoptosis (i.e., TNF-α, active caspase-3), and platelet activation, resulting in a reduction of infarct volume and improvement in neurobehavior in rats with cerebral ischemia. Therefore, this novel role of xanthohumol may represent high therapeutic potential for treatment or prevention of ischemia-reperfusion injury-related disorders.     

Consumption of lycopene inhibits the growth and progression of colon cancer in a mouse xenograft model

A previous study indicated that lycopene could significantly inhibit the proliferation of human colon cancer cells in vitro. However, the in vivo anticancer effects of lycopene against colon cancer have not been demonstrated yet. Therefore, this study investigated whether consumption of lycopene could prevent the growth and progression of colorectal tumor in a mouse xenograft model. Bioluminescence imaging, histopathological, immunofluorescence (IFC), and immunohistochemical (IHC) staining results indicated that lycopene could effectively suppress the growth and progression of colon cancer in tumor-bearing mice. The results demonstrated that lycopene significantly suppressed the nuclear expression of PCNA and β-catenin proteins in tumor tissues. Consumption of lycopene could also augment the E-cadherin adherent molecule and nuclear levels of cell cycle inhibitor p21(CIP1/WAF1) protein. The chemopreventive effects of lycopene were associated with suppression of COX-2, PGE(2), and phosphorylated ERK1/2 proteins. Furthermore, the inhibitory effects of lycopene were inversely correlated with the plasma levels of matrix metalloproteinase 9 (MMP-9) in tumor-bearing mice. These results suggested that lycopene could act as a chemopreventive agent against the growth and progression of colorectal cancer in a mouse xenograft model.     

Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3-carbinol, a major indole metabolite present in cruciferous vegetables

A variety of studies have suggested a cancer protective role of cruciferous vegetables. In the present study, we investigated the effect of indole-3-carbinol (I3C), a major indole metabolite in cruciferous vegetables, on cell proliferation and in vitro markers of angiogenesis in phorbol myristate acetate (PMA)-stimulated endothelial EA hy926 cells. The results showed that I3C inhibited the growth of EA hy926 cells in a concentration-dependent manner. The capillary-like tube formation by PMA-activated endothelial cells was significantly suppressed by I3C, and such inhibition was associated with decreased vascular endothelial growth factor (VEGF) and increased interleukin-8 (IL-8) secretion, but not with the expression of VEGF receptor-2 protein. Additionally, gelatin zymography analysis indicated that I3C suppressed activities of matrix metalloproteinases-2 (MMP-2) and MMP-9 stimulated by PMA. These results suggest that the dietary I3C may be useful in the treatment of human cancers and angiogenic diseases.     

Effects of black soybean [Glycine max (L.) Merr.] seed coats and its anthocyanidins on colonic inflammation and cell proliferation in vitro and in vivo

Anti-inflammatory and antiproliferative activities of anthocyanidins and anthocyanin-rich black soybean seed coats were studied in HT-29 human colon adenocarcinoma cells and carcinogen-treated F344 rats, respectively. Cyanidin and delphinidin significantly inhibited cell growth at concentrations of >or=1 microM. Anthocyanidins suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNAs in TPA-stimulated HT-29 cells. Both yellow and black soybean seed coat supplementation (10%, w/w) did not significantly reduce the number of aberrant crypt foci (ACF), although a modest decrease in the number of ACF was observed in animals fed soybean seed coats. The colonic COX-2 mRNA level was suppressed in rats fed both soybean seed coat diet. The plasma prostaglandin E 2 (PGE 2) level was reduced only in rats fed black soybean seed coats. No difference was observed in either colonic iNOS mRNA or plasma nitric oxide level. These results indicate that anthocyanidins are possible anti-inflammatory agents; however, further studies are required to determine required intake levels in vivo to exert antitumor effect.     

Activation of AMPK by pterostilbene suppresses lipogenesis and cell-cycle progression in p53 positive and negative human prostate cancer cells

Prostate cancer is one of the leading causes of cancer death in men in Western countries. Epidemiological studies have linked the consumption of fruits and vegetables to a reduced risk of prostate cancer, and small fruits are particularly rich sources of many active phytochemical stilbenes, such as pterostilbene. As a constituent of small fruits such as grapes, berries, and their products, pterostilbene is under intense investigation as a cancer chemopreventive agent. Using the p53 wild type LNCaP and p53 null PC3 cells, we found that treatment with pterostilbene resulted in dose-dependent inhibition of cellular proliferation, which suggested that the interaction of pterostilbene with the p53 might not fully explain its inhibitory effect on proliferation. In this study, we found that pterostilbene activated AMPK in both p53 positive and negative human prostate cancer cells. Pterostilbene-activated AMPK decreased the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the resolution between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive LNCaP cells, pterostilbene blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However, pterostilbene induced apoptosis in p53 negative PC3 cells. Our results suggest that pterostilbene may be a functional chemopreventive agent and that dietary exposure to pterostilbene would be helpful for antiprostate cancer activity.     

Ellagic Acid and Polyhydroxylated Urolithins Are Potent Catalytic Inhibitors of Human Topoisomerase II: An in Vitro Study

Ellagic acid (EA), a natural polyphenol abundant in fruits and common in our diet, is under intense investigation for its chemopreventive activity resulting from multiple effects. EA inhibits topoisomerase II, but the effects on the human enzyme of urolithins, its monolactone metabolites, are not known. Therefore, the action of several synthetic urolithins toward topoisomerases II was evaluated, showing that polyhydroxylated urolithins, EA, and EA-related compounds are potent inhibitors of the α and β isoforms of human topoisomerase II at submicromolar concentrations. Competition tests demonstrate a dose-dependent relationship between ATP and the inhibition of the enzyme. Docking experiments show that the active compounds bind the ATP pocket of the human enzyme, thus supporting the hypothesis that EA and polyhydroxylated urolithins act as ATP-competitive inhibitors of human topoisomerase II.     

Iberian pig as a model to clarify obscure points in the bioavailability and metabolism of ellagitannins in humans

Ellagitannin-containing foods (strawberries, walnuts, pomegranate, raspberries, oak-aged wine, etc.) have attracted attention due to their cancer chemopreventive, cardioprotective, and antioxidant effects. Ellagitannins (ETs) are not absorbed as such but are metabolized by the intestinal flora to yield urolithins (hydroxydibenzopyran-6-one derivatives). In this study, Iberian pig is used as a model to clarify human ET metabolism. Pigs were fed either cereal fodder or acorns, a rich source of ETs. Plasma, urine, bile, lumen and intestinal tissues (jejunum and colon), feces, liver, kidney, heart, brain, lung, muscle, and subcutaneous fat tissue were analyzed. The results demonstrate that acorn ETs release ellagic acid (EA) in the jejunum, then the intestinal flora metabolizes EA sequentially to yield tetrahydroxy- (urolithin D), trihydroxy- (urolithin C), dihydroxy- (urolithin A), and monohydroxy- (urolithin B) dibenzopyran-6-one metabolites, which were absorbed preferentially when their lipophilicity increased. Thirty-one ET-derived metabolites were detected, including 25 urolithin and 6 EA derivatives. Twenty-six extensively conjugated metabolites were detected in bile, glucuronides and methyl glucuronides of EA and particularly urolithin A, C, and D derivatives, confirming a very active enterohepatic circulation. Urolithins A and B as well as dimethyl-EA-glucuronide were detected in peripheral plasma. The presence of EA metabolites in bile and in urine and its absence in intestinal tissues suggested its absorption in the stomach. Urolithin A was the only metabolite detected in feces and together with its glucuronide was the most abundant metabolite in urine. No metabolites accumulated in any organ analyzed. The whole metabolism of ETs is shown for the first time, confirming previous studies in humans and explaining the long persistency of urolithin metabolites in the body mediated by an active enterohepatic circulation.     

60Co-g辐照改性银掺杂纳米TiO2及光催化降解乙烯

为了解60Co-射线辐照且以活性炭纤维(ACF)为载体所负载TiO2的半导体材料(TiO2/ACF)对光催化降解冷藏环境中乙烯的影响,该文拟采用60Co-辐照制备纳米Ag沉积的TiO2/ACF(Ag-TiO2/ACF)光催化材料,在模拟园艺产品的冷藏环境中,进行了3种不同膜的光催化降解乙烯效果的研究,并利用场发射扫描电镜(FESEM)、透射电子显微镜(TEM)、X射线衍射仪(XRD)对所制备的光催化材料进行相关的表征分析。结果表明:在加入分散剂聚乙烯吡咯烷酮后,60Co-辐照能使Ag颗粒较好地负载在TiO2上,TiO2均匀分散在ACF膜上而不发生团聚,且TiO2颗粒晶相改变、尺寸变小,有助于提高Ag-TiO2/ACF的催化效率。Ag-TiO2/ACF光催化降解乙烯的效果用一级动力学速率方程描述;经辐照制备的Ag-TiO2/ACF薄膜比未辐照的TiO2/ACF和辐照的TiO2/ACF薄膜光催化降解乙烯的反应速率常数分别提高了44%和37%。研究结果为TiO2光催化技术的进一步的应用提供了参考。     

Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland

Our group has shown in a phase II clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer (CaP) patients with a rising PSA. Ellagitannins (ETs) are the most abundant polyphenols present in PJ and contribute greatly towards its reported biological properties. On consumption, ETs hydrolyze to release ellagic acid (EA), which is then converted by gut microflora to 3,8-dihydroxy-6H-dibenzo[b, d]pyran-6-one (urolithin A, UA) derivatives. Despite the accumulating knowledge of ET metabolism in animals and humans, there is no available data on the pharmacokinetics and tissue disposition of urolithins. Using a standardized ET-enriched pomegranate extract (PE), we sought to further define the metabolism and tissue distribution of ET metabolites. PE and UA (synthesized in our laboratory) were administered to C57BL/6 wild-type male mice, and metabolite levels in plasma and tissues were determined over 24 h. ET metabolites were concentrated at higher levels in mouse prostate, colon, and intestinal tissues as compared to other tissues after administration of PE or UA. We also evaluated the effects of PE on CaP growth in severe combined immunodeficient (SCID) mice injected subcutaneously with human CaP cells (LAPC-4). PE significantly inhibited LAPC-4 xenograft growth in SCID mice as compared to vehicle control. Finally, EA and several synthesized urolithins were shown to inhibit the growth of human CaP cells in vitro. The chemopreventive potential of pomegranate ETs and localization of their bioactive metabolites in mouse prostate tissue suggest that pomegranate may play a role in CaP treatment and chemoprevention. This warrants future human tissue bioavailability studies and further clinical studies in men with CaP.