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Colloidal stabilities of polymer-coated nanosized zero-valent iron (pNZVI) and bare nanosized zero-valent iron (bNZVI) particles were investigated in the presence of groundwater solutes, such as Suwannee River natural organic matter (SRNOM), Pony Lake fulvic acid (PLFA), sodium ion, and calcium ion. Measurements of hydrodynamic diameter and zeta-potential showed that dissolved organic matters (SRNOM and PLFA) enhanced the stability of bNZVI particles, but that they did not affect the stability of pNZVI particles. These measurements also showed that the stability of pNZVI particles was inhibited by the cations but that the effect of the cations on bNZVI particles was inconclusive. The sedimentation test confirmed that the stability of pNZVI particles was inhibited by the sodium and calcium ions. The sedimentation test identified that the stability of bNZVI particles was inhibited only in the presence of calcium ion. The predictions on the stability of NZVI particles based on the Derjaguin–Landau–Verwey–Overbeek interaction energies were generally consistent with experimental observations. Energy barriers of bNZVI particles were estimated to be up to 7.5 and 91 kBTin the presence of PLFA and SRNOM, respectively. For pNZVI particles, energy barriers were present in all experimental conditions except for the suspension with calcium ion. [ABSTRACT FROM PUBLISHER]

The possibility of bank filtration as a water purification technique was assessed by comparing water quality of a river and bank filtrate obtained from a pilot plant operation during 7 months from November 2010 to May 2011. The research began with soil analysis, including soil adsorption characteristic, and then a comparison was performed in terms of total dissolved solids (TDS), suspended solids (SS), potassium permanganate (KMnO4) consumption, biological oxygen demand (BOD), and ammonium (NH4-N), nitrate (NO3-N), iron (Fe), and manganese (Mn) concentrations. The study area showed high concentrations of Fe (470 mg/kg), Mn (80 mg/kg), and NH4-N (15 mg/kg). The adsorption coefficients ofkand 1/nwere 0.00159 and 0.8714, respectively, which implied that adsorption of the soil depended on organic matter contents. Water quality comparisons revealed that TDS remained consistent, but SS was lower by 84% in bank filtration samples. NH4-N concentration increased from 0 mg/L to ≥ 1 mg/L possibly due to agricultural activities in the study area, while NO3-N concentration dropped to nearly 0 mg/L because of soil adsorption. Bank filtration reduced KMnO4consumption and BOD of river water by 54 and 71%, respectively. Concentrations of Fe and Mn significantly increased in bank filtration samples. [ABSTRACT FROM PUBLISHER]

Abstract: Red peppers and red pepper paste are reported to have anti-obesity, analgesic and anti-inflammatory effects in animals and humans due to the capsaicin in red pepper. We investigated whether consuming capsaicin and capsiate, a nonpungent capsaicin analogue, modifies glucose-stimulated insulin secretion, pancreatic β-cell survival and insulin sensitivity in 90% pancreatectomized (Px) diabetic rats, a moderate and non-obese type 2 diabetic animal model. Px diabetic rats were divided into 3 treatment groups: 1) capsaicin (Px-CPA), 2) capsiate (Px-CPI) or 3) dextrose (Px-CON) and provided high fat diets (40 energy % fat) containing assigned components (0.025% capsaicin, capsiate, or dextrose) for 8 weeks. Both capsaicin and capsiate reduced body weight gain, visceral fat accumulation, serum leptin levels and improved glucose tolerance without modulating energy intake in diabetic rats. In comparison to the control, both capsaicin and capsiate potentiated first and second and phase insulin secretion during hyperglycemic clamp. Both also increased β-cell mass by increasing proliferation and decreasing apoptosis of β-cells by potentiating insulin/IGF-1 signaling. However, only capsiate enhanced hepatic insulin sensitivity during euglycemic hyperinuslinemic clamp. Capsiate reduced hepatic glucose output and increased triglyceride accumulation in the hyperinsulinemic state and capsiate alone significantly increased glycogen storage. This was related to enhanced pAkt→PEPCK and pAMPK signaling. Capsaicin and capsiate reduced triglyceride storage through activating pAMPK. In conclusion, capsaicin and capsiate improve glucose homeostasis but they differently enhance insulin sensitivity in the liver, insulin secretion patterns, and islet morphometry in diabetic rats. Capsiate has better anti-diabetic actions than capsaicin. [Copyright &y& Elsevier]

Abstract: Auraptene is a citrus-derived natural monoterpene that has been shown to exert anti-cancer, anti-bacterial, anti-inflammatory, and antioxidant roles. Since little is known about other biological functions of auraptene, we examined the efficacy of auraptene for stimulating angiogenesis in human umbilical vein endothelial cells (HUVECs). Treatment with low concentrations of auraptene stimulated endothelial cell proliferation, migration, and tube formation. Furthermore, auraptene activated Erk, Akt, and endothelial nitric oxide synthase (eNOS), and increased NO production. Auraptene also partially induced the phosphorylation of VEGFR2. Furthermore, auraptene-induced activation of Erk, Akt, and eNOS were significantly inhibited by the inhibitors PD98059, LY294002, and l-NIO dihydrochloride. These results suggest that auraptene stimulates angiogenesis by regulating the VEGFR2, Erk, and PI3K/Akt-eNOS signaling pathways. [Copyright &y& Elsevier]

Recent studies suggest that phytoestrogens may exert a protective effect against osteoporosis. This study examined whether treatment with phytoestrogen extracts from Saururus chinensis (SC) exerted a preventive effect on estrogen-deficiency-induced osteoporosis. Six- to seven-month-old female Sprague-Dawley rats were randomly assigned into either a sham-operated group or one of three ovariectomy (OVX) subgroups: OVX treated with vehicle, OVX with alendronate, and OVX with SC extract (SC). Rats began receiving treatment 4 weeks before the OVX treatment and continued receiving treatment for an additional 10 weeks after OVX (for a combined total of 14 weeks). The results showed that the SC treatment prevented loss of femur bone mineral density after OVX, as determined by a significant decrease in the levels of serum bone turnover markers osteocalcin and alkaline phosphatase as well as urinary deoxypyridinoline. Micro-computed tomography analysis showed that the SC treatment significantly prevented decreases in bone volume/tissue volume, trabecular number and trabecular thickness, while also preventing an increase in trabecular separation. It was concluded that SC treatment could prevent OVX-induced loss of bone mass and deterioration in trabecular microarchitecture by suppressing bone turnover, thereby maintaining bone structural integrity. Further, no stimulation of proliferation of uterine tissue was noted. Therefore, it is suggested that treatment with S. chinensis extracts might be a potential alternative therapy for treating postmenopausal osteoporosis. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Decursin (De), an active component of Angelica gigas, is known to exert anticancer and neuroprotective effects. However, its antiobesity and antidiabetic potential has not yet been investigated. This study evaluated the antiobesity effect of decursin, particularly focusing on its ability to inhibit adipocyte differentiation in 3 T3-L1 cells. Decursin treatment resulted in the inhibition of adipocyte differentiation and the expression of fatty acid synthase. The study further investigated these antiobesity effects using mice fed a normal diet (ND), a high-fat diet (HFD) and a HFD plus decursin 200 mg/kg diet (HFD + De) for 7 weeks. Mice administered HFD plus decursin showed a drastic decrease in weight gain, triglyceride content, total cholesterol content and fat size compared with those that received the HFD alone; this was observed despite similar quantities of total food intake. Furthermore, decursin improved glucose tolerance in mice fed a HFD. Finally, administration of decursin along with the HFD significantly reduced the secretion of HFD-induced adipocytokines such as leptin, resistin, IL-6 and MCP-1. These results suggest that decursin might be useful for the treatment of obesity and diabetes. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Although soybeans have been shown to alleviate metabolic syndromes, fermented soybeans may have even greater effects. We investigated the antidiabetic effects of meju, a soy food that is fermented up to 2 mo, and the mechanism by which it exerts its effects. Methods: Meju was prepared by a traditional fermentation process: soybeans were fermented outdoors for 20 or 60 d. Methanol (M-60) and water (W-60) extracts from meju that had fermented for 60 d contained mostly isoflavonoid aglycones and small peptides, respectively, as opposed to mostly glycosylated isoflavonoids and proteins in the original soybeans. Results: Daidzein, M-60, and W-60 had better insulin-sensitizing actions by activating peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes than did unfermented soybeans. In addition, Min6 insulinoma cells treated with genistein, M-60, and W-60 had greater glucose-stimulated insulin secretion capacity and greater β-cell viability than those treated with unfermented soybeans. This improvement was associated with insulin/insulin-like growth factor-1 signaling that was activated by the tyrosine phosphorylation of insulin receptor substrate-2 and serine phosphorylation of Akt, and this in turn increased pancreatic and duodenal homeobox-1 expression. Furthermore, genistein, daidzein, and M-60 stimulated glucagon-like peptide-1 secretion in enteroendocrine NCI-H716 cells, which generated insulinotropic actions. Conclusion: The compositional changes in isoflavonoids and peptides that occurred during a longer fermentation period, without the use of salt, enhanced the antidiabetic effect of soybeans. [Copyright &y& Elsevier]

Abstract: Historically, the incidence of type 2 diabetes has been lower in Asian populations compared with those in Western countries. One possible reason for the lower incidence among Asians is that they consume fermented soybean products, which are unique to the traditional Asian diet. Some have hypothesized that dietary phytoestrogens and soy peptides in fermented soybean foods consumed in traditional Asian diets may help prevent and slow the progression of type 2 diabetes. This review evaluates the existing evidence from animal studies and clinical and epidemiologic investigations on fermented soybeans in the prevention and treatment of type 2 diabetes. Nutritional studies performed in animals and intervention studies with humans suggest that the ingestion of soy protein with isoflavones improves glucose control and reduces insulin resistance. Korean fermented soybean products such as doenjang, kochujang, and chungkookjang contain alterations in the structures and content of isoflavonoids and small bioactive peptides, which are produced during fermentation. Several studies revealed improvements in insulin resistance and insulin secretion with the consumption of these fermented products. Therefore, fermented soybean products may help prevent or attenuate the progression of type 2 diabetes. Although the lack of human intervention trials does not permit definitive conclusions, the evidence does suggest that fermented soy products may be better for preventing or delaying the progression of type 2 diabetes compared with nonfermented soybeans. [Copyright &y& Elsevier]

A reduced life span is an outcome associated with many prevalent diseases, including diabetes, obesity, and high blood pressure. In seeking to prevent these diseases, many researchers have looked into potential therapeutic benefits of naturally occurring compounds. AMP-activated protein kinase (AMPK) is a major metabolic-sensing protein implicated in the prevention of metabolic disorders, or in minimizing the effects thereof, via the regulation of both upstream and downstream target molecules. In the field of food and nutrition, the current focus lies in the finding of components that activate AMPK. AMPK is a serine/threonine protein kinase and is activated by several natural compounds, including resveratrol, epigallocatechin gallate, berberine, and quercetin. AMPK activation can induce ATP (adenosine triphosphate) generation through pathways such as glycolysis and β-oxidation. By contrast, ATP-consuming pathways, including fatty acid and cholesterol syntheses, and gluconeogenesis, are suppressed by AMPK activation. In this review, we will discuss how the activation of AMPK by naturally occurring compounds could help to prevent the development of numerous diseases; the potential mechanism underlying these effects will also be addressed. [Copyright &y& Elsevier]

The present study observed the effects of grape seed extract (GSE) and its ethylacetate (E) and ethylacetate/ethanol (EE) fractions on blood glucose levels in C57BL/KsJ-lepr db/lepr db ( db/db) mice at 4-12 weeks of age. In the GSE- and EE fraction-treated db/db group, the blood glucose concentration began to be lower than that in the vehicle-treated db/db group at 6 weeks after treatment, while the blood glucose concentration in the E fraction-treated db/db group was similar to that in the vehicle-treated db/db group. The glycosylated hemoglobin (HbA1c) level in the vehicle-treated db/db groups was 9.3%, whereas HbA1c levels in the GSE- and EE fraction-treated db/db group decreased significantly to 5.7% and 6.1%, respectively, at 8 weeks after treatment. However, administration of GSE and its EE fraction did not show any significant effects on body weights and food consumption in db/db mice. These results suggest that GSE and its EE fraction have a potential to decrease the blood glucose and HbA1c level, which is applicable to good healthy foods for reducing blood glucose levels. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study investigated the apoptotic regulation by green tea catechin epigallcatechin-3-gallate (EGCG) on colon cancer cells in the presence of low-dose H2O2 known to exert the activation of signal pathways leading to cell proliferation. In the presence of low-dose H2O2, EGCG induced apoptosis and abolished the cell-proliferative effect exhibited by low-dose H2O2. This reduction of growth was accompanied by an activation of AMP-activated kinase (AMPK), a decrease in cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) levels, and the induction of apoptotic markers such as p53 and poly(ADP-ribose) polymerase (PARP) cleavage. The low-dose H2O2 stimulated COX-2 expression, and treating cells with synthetic AMPK activator AICAR (5-aminoimiazole-4-carboxamide-1-β-d-ribofuranoside) resulted in greater suppression of COX-2 expression and PGE2. By treating cells with high concentrations of the reactive oxygen species (ROS) scavenger NAC ( N-acetyl-1-cysteine), the apoptotic effect of EGCG was abolished and led to suppression of AMPK and COX-2, indicating that the liberation of excessive ROS might be the upstream signal of the AMPK–COX-2 signaling pathway even in the presence of low-dose H2O2. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Red pepper and soybeans have been reported to modulate energy and glucose metabolism. However, the antidiabetic effect of kochujang, the fermented product of red pepper plus soybeans, has not been studied. We examined whether kochujang affected insulin secretion from β-cells and/or peripheral insulin resistance in 90% pancreatectomized diabetic rats fed high-fat diets. Methods: Diabetic rats consumed a high-fat diet containing two different kinds of 5% kochujang powder or the equivalent amount of nutrients for 8 wk. Two types of kochujang were made through the fermentation of two different kinds of meju (soybeans), red peppers, glutinous rice, and malts. Meju was produced by fermenting soybeans in a traditional method (TMK) or in a more modern method in which soybeans are inoculated with Bacillus subtilus and Aspergillus sojae (MMK). Results: TMK and MMK decreased body weight, visceral fat, and serum leptin levels without modulating caloric intake in diabetic rats compared with the control. TMK and MMK also improved glucose tolerance by enhancing insulin sensitivity but did not potentiate glucose-stimulated insulin secretion. The improvement in hepatic insulin sensitivity caused by TMK and MMK was explained by the potentiated phosphorylation of signal transducer and activator of transcription-3 → adenosine monophosphate kinase → acetyl-coenzyme A carboxylase and decreased phosphoenolpyruvate carboxykinase expression. Kochujang diets reduced hepatic glucose output and triacylglycerol accumulation and increased glycogen storage. Conclusion: The combination of red pepper and fermented soybeans in kochujang improves glucose homeostasis by reducing insulin resistance, not by enhancing β-cell function, in diabetic rats. The improvement is associated with decreased hepatic fat storage by the activation of adenosine monophosphate kinase. [Copyright &y& Elsevier]

Thee present study analysed the quantification of rutin in raw buckwheat extract (RBE) and germinated buckwheat extract (GBE) by high performance liquid chromatography (HPLC), and examined changes in body weight, systolic blood pressure (SBP) and nitrotyrosine (a marker for peroxynitrite formation) immunoreactivity in aortic endothelial cells in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats after treatment with RBE and GBE for 5 weeks. In the HPLC study, RBE and GBE contained a mean content of rutin of 1.52 ± 0.21 and 2.92 ± 0.88 mg/g, respectively. In the 600 mg/kg GBE-treated group, SBP was lower than that in the 600 mg/kg RBE-treated group. The treatment with RBE and/or GBE significantly reduced oxidative damage in aortic endothelial cells by lowering nitrotyrosine immunoreactivity. These results suggest that GBE has an antihypertensive effect and may protect arterial endothelial cells from oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the extracted substance of the fermented soybean paste (FSP) during fermentation through 1H Nuclear Magnetic Resonance Spectroscopy (NMR) and Principal Component Analysis (PCA). It mentions that the study has revealed the separation of 50% methanol extracts of the FSP through major compounds such as isoleucine, lactate, and glutamine. The result suggests that NMR and PCA are efficient techniques for ESP's metabolic profiling.

Ginsenosides, the active component of ginseng, exerts antidiabetic and anticancer effects. This study investigated the molecular basis of ginsenoside Rg3, a red ginseng rich constituent, focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. The data show that ginsenoside Rg3 was effective in the inhibition of adipocyte differentiation. This inhibitory effect of ginsenoside Rg3 on adipocyte differentiation was accompanied by PPAR-gamma inhibition in rosiglitazone-treated cells. The study also tested whether AMP-activated protein kinase (AMPK) activation was involved in the inhibitory effects of ginsenoside Rg3. AMPK plays a role in maintaining health in the context of diseases such as type 2 diabetes, obesity and cancer. AMPK was reported to control nutritional and hormonal signal modulating. Rg3 significantly and time-dependently activated AMPK. Taken together, these results suggest that the antiobesity effect of red ginseng rich constituent, ginsenoside Rg3, involves the AMPK signaling pathway and PPAR-gamma inhibition. [ABSTRACT FROM AUTHOR]

Ginsenosides, the active component of ginseng, exerts antidiabetic and anticancer effects. This study investigated the molecular basis of ginsenoside Rg3, a red ginseng rich constituent, focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. The data show that ginsenoside Rg3 was effective in the inhibition of adipocyte differentiation. This inhibitory effect of ginsenoside Rg3 on adipocyte differentiation was accompanied by PPAR- γ inhibition in rosiglitazone-treated cells. The study also tested whether AMP-activated protein kinase (AMPK) activation was involved in the inhibitory effects of ginsenoside Rg3. AMPK plays a role in maintaining health in the context of diseases such as type 2 diabetes, obesity and cancer. AMPK was reported to control nutritional and hormonal signal modulating. Rg3 significantly and time-dependently activated AMPK. Taken together, these results suggest that the antiobesity effect of red ginseng rich constituent, ginsenoside Rg3, involves the AMPK signaling pathway and PPAR- γ inhibition. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Scutellaria barbata D. Don (Lamiaceae; SB) inhibited the growth of leiomyomal cells (LM). A time-dependent antiproliferative effect was noted when 10−5 m buserelin, gonadotrophin-releasing hormone (GnRH) agonist or 20-40 µg/mL SB was added. The inhibition of cell growth decreased with the addition of the PKC activator (12-O-tetradecanoylphorbor-13-acetate; TPA) much as it did with the addition of SB, and the decreases in the viable cells caused by the addition of SB were reversed completely by pretreatment with a protein kinase C (PKC) inhibitor (calphostin C). The findings suggest that SB inhibits cell proliferation in cultured human uterine leiomyoma cells accompanied by PKC activation. Next, the study investigated the effect of SB on fetal development for toxicity. Pregnant Sprague-Dawley rats, from gestation day 6-15, were administered 20 g/L or 50 g/L SB in the drinking water and then killed on day 20. No maternal toxicity was observed, however, embryonic loss in the treatment groups was double that of the controls ( p < 0.05). No gross morphologic malformations were seen in the treated fetuses. Fetuses exposed to SB were found to be significantly heavier than the controls, an effect that was greater in female fetuses and was not correlated with increased placental size. The results suggest that the SB had no toxicity and that in utero exposure to SB resulted in increased early embryo loss with increased growth in surviving fetuses. On the other hand, Western blot analyses revealed that Bcl-2 protein of a 26 kDa was abundant in leiomyomal cells, but not in normal myometrial cells. The addition of progesterone (100 ng/mL) resulted in a striking increase in Bcl-2 protein expression in the cultured leiomyoma cells. However, the addition of SB (20 µg/mL) resulted in a significant reduction in Bcl-2 protein expression in the cells. The results indicated that human uterine leiomyomal cells express Bcl-2 protein and progesterone enhances its expression, however, SB reduces the expression of Bcl-2 protein in human uterine leiomyoma cells. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

It has been reported that the gum resin of Boswellia serrata (BS), which has been shown to have antiinflammatory properties, might also have anticancer effects. This study examined the potential of BS as an anticancer agent. The BS extract induces apoptosis in HeLa human cervical carcinoma cells, as confirmed by two apoptosis analyses, Hoechst staining and Annexin V/PI assay. Among the apoptosis pathways, the ER stress-associated mechanism was examined to determine its role in BS-induced apoptosis. The expression of GRP78 and CHOP, which are representatives of the ER stress proteins, and the calcium-binding protein-calpain were determined. The results showed significantly higher levels of both GRP78 and CHOP, and stronger calpain activity in the BS-treated cells than in the control cells. This shows that there is a correlation between ER stress signaling and apoptosis, which suggests the possibility of the BS–ER stress initiator as an anticancer therapeutic agent in human cervical carcinoma. [ABSTRACT FROM AUTHOR]

Scutellaria barbata D. Don (Lamiaceae) (SB) is a perennial herb, which is natively distributed throughout Korea and southern China. This herb is known in traditional Chinese medicine as Ban-Zhi-Lian and in traditional Korean medicine as Banjiryun. SB has been used as an antiinflammatory and antitumor agent. The SB showed strong growth-inhibitory activity and cancer chemopreventive activity in assays representing three major stages of carcinogenesis. The SB was found to act as an antimutagen; it mediated antiinflammatory effects; inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity). In addition, SB inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. On the other hand, an inhibitory effect of SB on the growth of gynecological cancer cell lines such as HeLa cell and human ovary cancer (HOC) was shown. When HOC cells were treated with SB, the expression of cyclooxygenase-2 was inhibited. These data suggest that SB merits investigation as a potential cancer chemopreventive agent in humans, especially in gynecological cancers. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The vascular relaxant effect of the rhizome extract of Rheum undulatum was evaluated with isolated rat thoracic aorta preparations. The methanol extract of the rhizome induced a concentration-dependent relaxation of aortic preparations precontracted with 0.3 µ m phenylephrine (EC50 value: 5.8 µg/mL). The activity-guided fractionation of the extract led to the isolation of seven hydroxystilbene components as active principles, i.e. piceatannol, resveratrol, desoxyrhapontigenin, rhapontigenin, piceid, rhaponticin and ε-viniferin. Of these, piceatannol, a tetrahydroxystilbene, exhibited the most potent vascular relaxant effect in rat aortic preparations (EC50 value 2.4 µ m). The vasorelaxant effect of piceatannol on endothelium-intact aorta rings was diminished completely by the removal of functional endothelium or by pretreatment of the aortic tissues with NG-nitro- l-arginine methyl ester. These results suggest that piceatannol may be the major mediator responsible for the vasorelaxing properties of the rhizome extract of Rheum undulatum and the vasorelaxant effects of the piceatannol may be mediated via endothelium-dependent nitric oxide signaling pathway. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

3,3'-Diindolylmethane (DIM) is the major in vivo product of acid-catalyzed oligomerization of indole-3-carbinol, which is a promising anticancer agent present in cruciferous vegetables and has itself been reported to have anticarcinogenic properties. This study examined DIM-mediated regulation of apoptosis in the HCT116 (wild-type p53) and HT-29 (mutant p53) human colon cancer cell lines. DIM (0-30 micromol/L) substantially decreased the number of viable cells and induced apoptosis of HCT116 and HT-29 cells in a concentration-dependent manner. Western-blot analyses of total cell lysates revealed that DIM increased the activation of caspase-3, -7, -8, and -9 and enhanced poly(ADP-ribose) polymerase cleavage in both HCT116 and HT-29 cells. In addition, DIM increased the translocation of cytochrome c and Smac/Diablo from the mitochondria to the cytoplasm. In concert with the caspase-8 activation by DIM, increased levels of Fas and truncated Bid were observed. DIM did not affect the protein levels of p53, Bcl-2, Bax, or Fas ligand (FasL) in HCT116 cells. In HT-29 cells, however, DIM decreased Bcl-2 levels, although the protein levels of Bax or FasL were not affected. The caspase-8 inhibitor Z-IETD-FMK attenuated the DIM-induced apoptosis, indicating that increased activation of this enzyme contributed to the increase in p53-independent apoptosis that was observed in colon cancer cells. We have demonstrated that DIM induces apoptosis in colon cancer cells, providing insights into the mechanisms underlying its antitumorigenic activities. [ABSTRACT FROM AUTHOR]

Fisetin, a natural flavonol present in edible vegetables, fruits, and wine, was reported to exert anticarcinogenic effects. The objective of the current study was to examine the effect of fisetin on the cell cycle progression of the human colon cancer cell line HT-29. HT-29 cells were cultured in serum-free medium with 0, 20, 40, or 60 micromol/L fisetin. Fisetin dose dependently inhibited both cell growth and DNA synthesis (P < 0.05), with a 79 +/- 1% decrease in cell number observed 72 h after the addition of 60 micromol/L fisetin. Perturbed cell cycle progression from the G(1) to S phase was observed at 8 h with 60 micromol/L fisetin treatment, whereas a G(2)/M phase arrest was observed after 24 h (P < 0.05). The phosphorylation state of the retinoblastoma proteins shifted from hyperphosphorylated to hypophosphorylated in cells treated with 40 micromol/L fisetin. (P < 0.05). Fisetin decreased the activities of cyclin-dependent kinases (CDK)2 and CDK4; these effects were likely attributable to decreases in the levels of cyclin E and D1 and an increase in p21(CIP1/WAF1) levels (P < 0.05). However, fisetin also inhibited CDk4 activity in a cell-free system (P < 0.05), indicating that it may directly inhibit CDk4 activity. The protein levels of cell division cycles (CDC)2 and CDC25C and the activity of CDC2 were also decreased in fisetin-treated cells (P < 0.05). These results indicate that inhibition of cell cycle progression in HT-29 cells after treatment with fisetin can be explained, at least in part, by modification of CDK activities. [ABSTRACT FROM AUTHOR]