Curcumin synergizes with resveratrol to inhibit colon cancer.

Science.gov (United States)

Majumdar, Adhip P N; Banerjee, Sanjeev; Nautiyal, Jyoti; Patel, Bhaumik B; Patel, Vaishali; Du, Jianhua; Yu, Yingjie; Elliott, Althea A; Levi, Edi; Sarkar, Fazlul H

2009-01-01

Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.

Dietary tocopherols inhibit PhIP-induced prostate carcinogenesis in CYP1A-humanized mice.

Science.gov (United States)

Chen, Jayson X; Li, Guangxun; Wang, Hong; Liu, Anna; Lee, Mao-Jung; Reuhl, Kenneth; Suh, Nanjoo; Bosland, Maarten C; Yang, Chung S

2016-02-01

Tocopherols, the major forms of vitamin E, exist as alpha-tocopherol (α-T), β-T, γ-T and δ-T. The cancer preventive activity of vitamin E is suggested by epidemiological studies, but recent large-scale cancer prevention trials with high dose of α-T yielded disappointing results. Our hypothesis that other forms of tocopherols have higher cancer preventive activities than α-T was tested, herein, in a novel prostate carcinogenesis model induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a dietary carcinogen, in the CYP1A-humanized (hCYP1A) mice. Treatment of hCYP1A mice with PhIP (200 mg/kg b.w., i.g.) induced high percentages of mouse prostatic intraepithelial neoplasia (mPIN), mainly in the dorsolateral glands. Supplementation with a γ-T-rich mixture of tocopherols (γ-TmT, 0.3% in diet) significantly inhibited the development of mPIN lesions and reduced PhIP-induced elevation of 8-oxo-deoxyguanosine, COX-2, nitrotyrosine, Ki-67 and p-AKT, and the loss of PTEN and Nrf2. Further studies with purified δ-T, γ-T or α-T (0.2% in diet) showed that δ-T was more effective than γ-T or α-T in preventing mPIN formations and p-AKT elevation. These results indicate that γ-TmT and δ-T could be effective preventive agents of prostate cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Inhibitory Effect of a γ-Tocopherol-Rich Mixture of Tocopherols on the Formation and Growth of LNCaP Prostate Tumors in Immunodeficient Mice

Energy Technology Data Exchange (ETDEWEB)

Zheng, Xi, E-mail: xizheng@rci.rutgers.edu [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States); Cui, Xiao-Xing [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Khor, Tin Oo; Huang, Ying [Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (United States); DiPaola, Robert S; Goodin, Susan [Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States); Lee, Mao-Jung [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Yang, Chung S [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States); Kong, Ah-Ng [Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States); Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (United States); Allan H, Conney [Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Cancer Institute of New Jersey, New Brunswick, NJ 08903 (United States)

2011-09-28

In the present study, we determined the effects of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) on the growth and apoptosis of cultured human prostate cancer LNCaP cells. We also determined the effects of dietary γ-TmT on the formation and growth of LNCaP tumors in immunodeficient mice. In the in vitro study, we found that the activity of γ-TmT was stronger than α-tocopherol for inhibiting the growth and stimulating apoptosis in LNCaP cells. In the animal study, treatment of severe combined immunodeficient (SCID) mice with dietary γ-TmT inhibited the formation and growth of LNCaP xenograft tumors in a dose-dependent manner. Mechanistic studies showed that γ-TmT administration inhibited proliferation as reflected by decreased mitosis and stimulated apoptosis as reflected by increased caspase-3 (active form) expression in LNCaP tumors. In addition, dietary administration of γ-TmT increased the levels of α-, γ- and δ- tocopherol in plasma, and increased levels of γ- and δ- tocopherol were also observed in the prostate and in tumors. The present study demonstrated that γ-TmT had strong anticancer activity both in vitro and in vivo. Additional studies are needed to determine the potential preventive effect of γ-TmT for prostate cancer in humans.

Inhibitory Effect of a γ-Tocopherol-Rich Mixture of Tocopherols on the Formation and Growth of LNCaP Prostate Tumors in Immunodeficient Mice

International Nuclear Information System (INIS)

Zheng, Xi; Cui, Xiao-Xing; Khor, Tin Oo; Huang, Ying; DiPaola, Robert S; Goodin, Susan; Lee, Mao-Jung; Yang, Chung S; Kong, Ah-Ng; Allan H, Conney

2011-01-01

In the present study, we determined the effects of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) on the growth and apoptosis of cultured human prostate cancer LNCaP cells. We also determined the effects of dietary γ-TmT on the formation and growth of LNCaP tumors in immunodeficient mice. In the in vitro study, we found that the activity of γ-TmT was stronger than α-tocopherol for inhibiting the growth and stimulating apoptosis in LNCaP cells. In the animal study, treatment of severe combined immunodeficient (SCID) mice with dietary γ-TmT inhibited the formation and growth of LNCaP xenograft tumors in a dose-dependent manner. Mechanistic studies showed that γ-TmT administration inhibited proliferation as reflected by decreased mitosis and stimulated apoptosis as reflected by increased caspase-3 (active form) expression in LNCaP tumors. In addition, dietary administration of γ-TmT increased the levels of α-, γ- and δ- tocopherol in plasma, and increased levels of γ- and δ- tocopherol were also observed in the prostate and in tumors. The present study demonstrated that γ-TmT had strong anticancer activity both in vitro and in vivo. Additional studies are needed to determine the potential preventive effect of γ-TmT for prostate cancer in humans

Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

Directory of Open Access Journals (Sweden)

Cheng M

2014-12-01

Full Text Available Michelle Cheng,1,* Samantha Ho,1,* Jun Hwan Yoo,1,2,* Deanna Hoang-Yen Tran,1,* Kyriaki Bakirtzi,1 Bowei Su,1 Diana Hoang-Ngoc Tran,1 Yuzu Kubota,1 Ryan Ichikawa,1 Hon Wai Koon1 1Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Republic of Korea *These authors share co-first authorship Background: Cathelicidin (LL-37 in humans and mCRAMP in mice represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the

Supplemental and highly-elevated tocopherol doses differentially regulate allergic inflammation: reversibility of α-tocopherol and γ-tocopherol's effects

Science.gov (United States)

McCary, Christine A.; Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Cook-Mills, Joan M.

2011-01-01

We have reported that supplemental doses of the α- and γ-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with antigen and supplemental tocopherols in a first phase of treatment followed by a 4 week clearance phase and then the mice received a second phase of antigen and tocopherol treatments. The pro-inflammatory effects of supplemental levels of γ-tocopherol in phase 1 were only partially reversed by supplemental α-tocopherol in phase 2 but were completely reversed by raising α-tocopherol levels 10-fold in phase 2. When γ-tocopherol levels were increased 10-fold (highly-elevated tocopherol) so that the lung tissue γ-tocopherol levels were equal to the lung tissue levels of supplemental α-tocopherol, γ-tocopherol reduced leukocyte numbers in the lung lavage fluid. In contrast to the lung lavage fluid, highly-elevated levels of γ-tocopherol increased inflammation in the lung tissue. These regulatory effects of highly-elevated tocopherols on tissue inflammation and lung lavage fluid were reversible in a second phase of antigen challenge without tocopherols. In summary, the pro-inflammatory effects of supplemental γ-tocopherol on lung inflammation were partially reversed by supplemental levels of α-tocopherol but were completely reversed by highly-elevated-levels of α-tocopherol. Also, highly-elevated levels of γ-tocopherol were inhibitory and reversible in lung lavage but, importantly, were pro-inflammatory in lung tissue sections. These results have implications for future studies with tocopherols and provide a new context in which to review vitamin E studies in the literature. PMID:21317387

α-Tocopherol impact on oxy-radical induced free radical decomposition of DMSO: Spin trapping EPR and theoretical studies

International Nuclear Information System (INIS)

Jerzykiewicz, Maria; Cwielag-Piasecka, Irmina; Witwicki, Maciej; Jezierski, Adam

2011-01-01

Graphical abstract: α-Tocopherol inhibits the oxidation of ·CH 3 to ·OCH 3 . Display Omitted Highlights: → α-Tocopherol does not inhibit the oxidation of DMSO to ·CH 3 . → α-Tocopherol inhibits the oxidation of ·CH 3 to ·OCH 3 . → α-Tocopherol does not inhibit the oxidation of PBN. → The structures of observed spin adducts were theoretically confirmed. - Abstract: EPR spin trapping and theoretical methods such as density functional theory (DFT) as well as combined DFT and quadratic configuration interaction approach (DFT/QCISD) were used to identify the radicals produced in the reaction of oxy-radicals and dimethyl sulfoxide (DMSO) in the presence and absence of α-tocopherol. Additionally, the mixtures of α-tocopherol with linolenic acid and glyceryl trilinoleate as well as bioglycerols (glycerol fractions from biodiesel production) were tested. α-Tocopherol inhibited oxidation of the main decomposition product of DMSO, ·CH 3 to ·OCH 3 but did not prevent the transformation process of N-t-butyl-α-phenylnitrone (PBN) into 2-methyl-2-nitrosopropane (MNP). Theoretical investigations confirmed the structures of proposed spin adducts and allowed to correlate the EPR parameters observed in the experiment with the spin adducts electronic structure.

Alpha-tocopherol inhibits pore formation in oxidized bilayers

NARCIS (Netherlands)

Boonnoy, P.; Karttunen, M.; Wong-Ekkabut, J.

2017-01-01

In biological membranes, alpha-tocopherols (α-toc; vitamin E) protect polyunsaturated lipids from free radicals. Although the interactions of α-toc with non-oxidized lipid bilayers have been studied, their effects on oxidized bilayers remain unknown. In this study, atomistic molecular dynamics (MD)

{alpha}-Tocopherol impact on oxy-radical induced free radical decomposition of DMSO: Spin trapping EPR and theoretical studies

Energy Technology Data Exchange (ETDEWEB)

Jerzykiewicz, Maria, E-mail: Mariaj@wchuwr.pl [Faculty of Chemistry, Wroclaw University, 14 F. Joliot-Curie St., 50-383 Wroclaw (Poland); Cwielag-Piasecka, Irmina; Witwicki, Maciej; Jezierski, Adam [Faculty of Chemistry, Wroclaw University, 14 F. Joliot-Curie St., 50-383 Wroclaw (Poland)

2011-05-26

Graphical abstract: {alpha}-Tocopherol inhibits the oxidation of {center_dot}CH{sub 3} to {center_dot}OCH{sub 3}. Display Omitted Highlights: {yields} {alpha}-Tocopherol does not inhibit the oxidation of DMSO to {center_dot}CH{sub 3}. {yields} {alpha}-Tocopherol inhibits the oxidation of {center_dot}CH{sub 3} to {center_dot}OCH{sub 3}. {yields} {alpha}-Tocopherol does not inhibit the oxidation of PBN. {yields} The structures of observed spin adducts were theoretically confirmed. - Abstract: EPR spin trapping and theoretical methods such as density functional theory (DFT) as well as combined DFT and quadratic configuration interaction approach (DFT/QCISD) were used to identify the radicals produced in the reaction of oxy-radicals and dimethyl sulfoxide (DMSO) in the presence and absence of {alpha}-tocopherol. Additionally, the mixtures of {alpha}-tocopherol with linolenic acid and glyceryl trilinoleate as well as bioglycerols (glycerol fractions from biodiesel production) were tested. {alpha}-Tocopherol inhibited oxidation of the main decomposition product of DMSO, {center_dot}CH{sub 3} to {center_dot}OCH{sub 3} but did not prevent the transformation process of N-t-butyl-{alpha}-phenylnitrone (PBN) into 2-methyl-2-nitrosopropane (MNP). Theoretical investigations confirmed the structures of proposed spin adducts and allowed to correlate the EPR parameters observed in the experiment with the spin adducts electronic structure.

Hypoxia inhibits colonic ion transport via activation of AMP kinase.

LENUS (Irish Health Repository)

Collins, Danielle

2012-02-01

BACKGROUND AND AIMS: Mucosal hypoxia is a common endpoint for many pathological processes including ischemic colitis, colonic obstruction and anastomotic failure. Previous studies suggest that hypoxia modulates colonic mucosal function through inhibition of chloride secretion. However, the molecular mechanisms underlying this observation are poorly understood. AMP-activated protein kinase (AMPK) is a metabolic energy regulator found in a wide variety of cells and has been linked to cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride secretion in several different tissues. We hypothesized that AMPK mediates many of the acute effects of hypoxia on human and rat colonic electrolyte transport. METHODS: The fluorescent chloride indicator dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used to measure changes in intracellular chloride concentrations in isolated single rat colonic crypts. Ussing chamber experiments in human colonic mucosa were conducted to evaluate net epithelial ion transport. RESULTS: This study demonstrates that acute hypoxia inhibits electrogenic chloride secretion via AMPK mediated inhibition of CFTR. Pre-treatment of tissues with the AMPK inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo [1,5-a] pyrimidine (compound C) in part reversed the effects of acute hypoxia on chloride secretion. CONCLUSION: We therefore suggest that AMPK is a key component of the adaptive cellular response to mucosal hypoxia in the colon. Furthermore, AMPK may represent a potential therapeutic target in diseased states or in prevention of ischemic intestinal injury.

Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol.

OpenAIRE

Cooney, R V; Franke, A A; Harwood, P J; Hatch-Pigott, V; Custer, L J; Mordan, L J

1993-01-01

In the vitamin E group, alpha-tocopherol is generally considered to be the most potent antioxidant with the highest vitamin bioactivity, yet gamma-tocopherol is produced in greater amounts by many plants and is the principal tocopherol in the United States diet. This report describes a fundamental difference in the chemical reactivities of alpha-tocopherol and gamma-tocopherol with nitrogen dioxide (NO2), which leads to the formation of a nitrosating agent from alpha-tocopherol, but not from ...

Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

Science.gov (United States)

He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

2014-02-01

Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

The effect of γ-tocopherol on proliferation, integrin expression, adhesion, and migration of human glioma cells

International Nuclear Information System (INIS)

Samandari, Elika; Visarius, Theresa; Zingg, Jean-Marc; Azzi, Angelo

2006-01-01

The effect of vitamin E on proliferation, integrin expression, adhesion, and migration in human glioma cells has been studied. γ-tocopherol at 50 μM concentration exerted more inhibitory effect than α-tocopherol at the same concentration on glioma cell proliferation. Integrin α5 and β1 protein levels were increased upon both α- and γ-tocopherol treatments. In parallel, an increase in the α5β1 heterodimer cell surface expression was observed. The tocopherols inhibited glioma cell-binding to fibronectin where γ-tocopherol treatment induced glioma cell migration. Taken together, the data reported here are consistent with the notion that the inhibition of glioma cell proliferation induced by tocopherols may be mediated, at least in part, by an increase in integrin α5 and β1 expression. Cell adhesion is also negatively affected by tocopherols, despite a small increase in the surface appearance of the α5β1 heterodimer. Cell migration is stimulated by γ-tocopherol. It is concluded that α5 and β1 integrin expression and surface appearance are not sufficient to explain all the observations and that other integrins or in general other factors may be associated with these events

Lipoperoxides, alpha-tocopherol and ceruloplasmin in gamma-irradiated blood plasma

International Nuclear Information System (INIS)

Aladzhov, E.; Popzakharieva, V.

1995-01-01

Ceruloplasmin, alpha-tocopherol and lipid peroxide concentrations are evaluated in blood plasma for transfusion following exposure to irradiation with 60 Co gamma rays at doses 23, 50, 100 and 200 Gy. In plasma exposed to irradiation an increase in lipid peroxides and decrease in alpha-tocopherol and ceruloplasmin are observed. The addition of 2.3 U/ml ceruloplasmin to plasma prior to irradiation reduces the quantity of lipid peroxides and protects alpha-tocopherol. The possible explanation is that the metal helates prevent the formation of free hydroxyl radicals and thus inhibit the oxidation of lipid membranes. 15 refs., 1 tab. (author)

Red meat and colon cancer : dietary haem-induced colonic cytotoxicity and epithelial hyperproliferation are inhibited by calcium

NARCIS (Netherlands)

Sesink, ALA; Termont, DSML; Kleibeuker, JH; Van der Meer, R

2001-01-01

High intake of red meat is associated with increased colon cancer risk. We have shown earlier that this may be due to the high haem content of red meat, because dietary haem increased cytolytic activity of faecal water and colonic epithelial proliferation. Dietary calcium inhibits diet-induced

Increased antioxidant efficacy of tocopherols by surfactant solubilization in oil-in-water emulsions.

Science.gov (United States)

Kiralan, S Sezer; Doğu-Baykut, Esra; Kittipongpittaya, Ketinun; McClements, David Julian; Decker, Eric A

2014-10-29

The physical location of antioxidants in oil-in-water emulsions can have significant influence on their free radical scavenging activity and ability to inhibit lipid oxidation. We aimed to determine the effect of the surfactant concentration on the partitioning behavior of tocopherols (α, γ, and δ) in oil-in-water emulsions. Tween 20 (0.1, 0.5, and 1%) increased the partitioning of the tocopherols into the aqueous phase via the formation of Tween 20-tocopherol comicelles. Partitioning behavior of antioxidants was dependent upon the number of methyl groups and, thus, polarity of the tocopherols. δ-Tocopherol (one methyl group) exhibited the most partitioning into the aqueous phase, while α-tocopherol (three methyl groups) had the lowest partitioning. Lipid oxidation studies showed that the antioxidant activity of δ- and α-tocopherols was enhanced by adding Tween 20 to oil-in-water emulsions. This work suggests that surfactant micelles could increase the antioxidant activity of tocopherols by changing their physical location.

Chemopreventive activity of vitamin E in breast cancer: a focus on γ- and δ-tocopherol.

Science.gov (United States)

Smolarek, Amanda K; Suh, Nanjoo

2011-11-01

Vitamin E consists of eight different variants: α-, β-, γ-, and δ-tocopherols (saturated phytyl tail) and α-, β-, γ-, and δ-tocotrienols (unsaturated phytyl tail). Cancer prevention studies with vitamin E have primarily utilized the variant α-tocopherol. To no avail, a majority of these studies focused on variant α-tocopherol with inconsistent results. However, γ-tocopherol, and more recently δ-tocopherol, have shown greater ability to reduce inflammation, cell proliferation, and tumor burden. Recent results have shown that γ-enriched mixed tocopherols inhibit the development of mammary hyperplasia and tumorigenesis in animal models. In this review, we discuss the possible differences between the variant forms, molecular targets, and cancer-preventive effects of tocopherols. We recommend that a γ-enriched mixture, γ- and δ-tocopherol, but not α-tocopherol, are promising agents for breast cancer prevention and warrant further investigation.

Enzymatic sulfation of tocopherols and tocopherol metabolites by human cytosolic sulfotransferases.

Science.gov (United States)

Hashiguchi, Takuyu; Kurogi, Katsuhisa; Sakakibara, Yoichi; Yamasaki, Masao; Nishiyama, Kazuo; Yasuda, Shin; Liu, Ming-Cheh; Suiko, Masahito

2011-01-01

Tocopherols are essential micronutrients for mammals widely known as potent lipid-soluble antioxidants that are present in cell membranes. Recent studies have demonstrated that most of the carboxychromanol (CEHC), a tocopherol metabolite, in the plasma exists primarily in sulfate- and glucuronide-conjugated forms. To gain insight into the enzymatic sulfation of tocopherols and their metabolites, a systematic investigation was performed using all 14 known human cytosolic sulfotransferases (SULTs). The results showed that the members of the SULT1 family displayed stronger sulfating activities toward tocopherols and their metabolites. These enzymes showed a substrate preference for γ-tocopherol over α-tocopherol and for γ-CEHC over other CEHCs. Using A549 human lung epithelial cells in a metabolic labeling study, a similar trend in the sulfation of tocopherols and CEHCs was observed. Collectively, the results obtained indicate that SULT-mediated enzymatic sulfation of tocopherols and their metabolites is a significant pathway for regulation of the homeostasis and physiological functions of these important compounds.

MiR-34a inhibits colon cancer proliferation and metastasis by inhibiting platelet-derived growth factor receptor α.

Science.gov (United States)

Li, Chunyan; Wang, Yulin; Lu, Shuming; Zhang, Zhuqing; Meng, Hua; Liang, Lina; Zhang, Yan; Song, Bo

2015-11-01

The microRNA (miRNA), miR‑34a is significant in colon cancer progression. In the present study, the role of miR‑34a in colon cancer cell proliferation and metastasis was investigated. It was found that the expression of miR‑34a in colon cancer tissues and cell lines was lower when compared with that of normal tissues and cells. Further research demonstrated that miR‑34a inhibited cell proliferation, induced G1 phase arrest, and suppressed metastasis and epithelial mesenchymal transition in colon cancer cells. Bioinformatic prediction indicated that platelet‑derived growth factor receptor α (PDGFRA) was a potential target gene of miR‑34a and a luciferase assay identified that PDGFRA was a novel direct target gene of miR‑34a. In addition, assays of western blot analyses and quantitative reverse‑transcription polymerase chain reaction confirmed that miR‑34a decreased PDGFRA mRNA expression and protein levels in colon cancer cells. Assessment of cellular function indicated that miR‑34a inhibited colon cancer progression via PDGFRA. These findings demonstrate that miR‑34a may act as a negative regulator in colon cancer by targeting PDGFRA.

Tocopherols in cancer: An update.

Science.gov (United States)

Das Gupta, Soumyasri; Suh, Nanjoo

2016-06-01

Tocopherols exist in four forms designated as α, β, δ, and γ. Due to their strong antioxidant properties, tocopherols have been suggested to reduce the risk of cancer. Cancer prevention studies with tocopherols have mostly utilized α-tocopherol. Large-scale clinical trials with α-tocopherol provided inconsistent results regarding the cancer-preventive activities of tocopherols. This review summarizes our current understanding of the anticancer activities of different forms of tocopherols based on follow-up of the clinical trials, recent epidemiological evidences, and experimental studies using in vitro and in vivo models. The experimental data provide strong evidence in support of the anticancer activities of δ-tocopherol, γ-tocopherol, and the natural tocopherol mixture rich in γ-tocopherol, γ-TmT, over α-tocopherol. Such outcomes emphasize the need for detailed investigation into the cancer-preventive activities of different forms of tocopherols to provide a strong rationale for intervention studies in the future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative Effects of Biodynes, Tocotrienol-Rich Fraction, and Tocopherol in Enhancing Collagen Synthesis and Inhibiting Collagen Degradation in Stress-Induced Premature Senescence Model of Human Diploid Fibroblasts

Science.gov (United States)

Jam, Faidruz Azura; Ismail, Zahariah; Wan Ngah, Wan Zurinah

2013-01-01

Biodynes, tocotrienol-rich fraction (TRF), and tocopherol have shown antiaging properties. However, the combined effects of these compounds on skin aging are yet to be investigated. This study aimed to elucidate the skin aging effects of biodynes, TRF, and tocopherol on stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs) by determining the expression of collagen and MMPs at gene and protein levels. Primary HDFs were treated with biodynes, TRF, and tocopherol prior to hydrogen peroxide (H2O2) exposure. The expression of COL1A1, COL3A1, MMP1, MMP2, MMP3, and MMP9 genes was determined by qRT-PCR. Type I and type III procollagen proteins were measured by Western blotting while the activities of MMPs were quantified by fluorometric Sensolyte MMP Kit. Our results showed that biodynes, TRF, and tocopherol upregulated collagen genes and downregulated MMP genes (P < 0.05). Type I procollagen and type III procollagen protein levels were significantly increased in response to biodynes, TRF, and tocopherol treatment (P < 0.05) with reduction in MMP-1, MMP-2, MMP-3, and MMP-9 activities (P < 0.05). These findings indicated that biodynes, TRF, and tocopherol effectively enhanced collagen synthesis and inhibited collagen degradation and therefore may protect the skin from aging. PMID:24396567

Comparative Effects of Biodynes, Tocotrienol-Rich Fraction, and Tocopherol in Enhancing Collagen Synthesis and Inhibiting Collagen Degradation in Stress-Induced Premature Senescence Model of Human Diploid Fibroblasts

Directory of Open Access Journals (Sweden)

Suzana Makpol

2013-01-01

Full Text Available Biodynes, tocotrienol-rich fraction (TRF, and tocopherol have shown antiaging properties. However, the combined effects of these compounds on skin aging are yet to be investigated. This study aimed to elucidate the skin aging effects of biodynes, TRF, and tocopherol on stress-induced premature senescence (SIPS model of human diploid fibroblasts (HDFs by determining the expression of collagen and MMPs at gene and protein levels. Primary HDFs were treated with biodynes, TRF, and tocopherol prior to hydrogen peroxide (H2O2 exposure. The expression of COL1A1, COL3A1, MMP1, MMP2, MMP3, and MMP9 genes was determined by qRT-PCR. Type I and type III procollagen proteins were measured by Western blotting while the activities of MMPs were quantified by fluorometric Sensolyte MMP Kit. Our results showed that biodynes, TRF, and tocopherol upregulated collagen genes and downregulated MMP genes (P<0.05. Type I procollagen and type III procollagen protein levels were significantly increased in response to biodynes, TRF, and tocopherol treatment (P<0.05 with reduction in MMP-1, MMP-2, MMP-3, and MMP-9 activities (P<0.05. These findings indicated that biodynes, TRF, and tocopherol effectively enhanced collagen synthesis and inhibited collagen degradation and therefore may protect the skin from aging.

Impact of Phospholipids and Tocopherols on the Oxidative Stability of Soybean Oil-in-Water Emulsions.

Science.gov (United States)

Samdani, Gautam K; McClements, D Julian; Decker, Eric A

2018-04-18

Phospholipids have been shown to act synergistically with tocopherols and delay lipid oxidation in bulk oil. The synergistic activity between phospholipids and tocopherols is due to the ability of amino-group-containing phospholipids (e.g., phosphatidylethanolamine (PE) and phosphatidylserine (PS)) to convert oxidized tocopherol back into tocopherols. This study shows the effect of PE and PS on the antioxidant activity of different tocopherol homologues in oil-in-water emulsions. Effect of emulsifier type on the interaction between tocopherols and phospholipids was also studied. δ-Tocopherol and PE exhibited greater antioxidant activity as compared to α-tocopherol and PE. PS displayed 1.5-3 times greater synergism than PE with Tween 20 as emulsifier whereas both PE and PS had a similar antioxidant activity in the presence of α-tocopherol when bovine serum albumin was used as the emulsifier. This study is the first to show that PE and PS can act synergistically with tocopherols to inhibit lipid oxidation in oil-in-water emulsions and can present a new clean label antioxidant strategy for food emulsions.

Supplemental and highly-elevated tocopherol doses differentially regulate allergic inflammation: reversibility of α-tocopherol and γ-tocopherol's effects

OpenAIRE

McCary, Christine A.; Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Cook-Mills, Joan M.

2011-01-01

We have reported that supplemental doses of the α- and γ-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with antigen and supplemental tocopherols in a first phase of treatment followed by a 4 week clearance phase and then the mice received a second phase of antigen and tocopherol treatments. The pro-inflammatory effects of supplement...

Piriformospora indica root colonization triggers local and systemic root responses and inhibits secondary colonization of distal roots.

Science.gov (United States)

Pedrotti, Lorenzo; Mueller, Martin J; Waller, Frank

2013-01-01

Piriformosporaindica is a basidiomycete fungus colonizing roots of a wide range of higher plants, including crop plants and the model plant Arabidopsis thaliana. Previous studies have shown that P. indica improves growth, and enhances systemic pathogen resistance in leaves of host plants. To investigate systemic effects within the root system, we established a hydroponic split-root cultivation system for Arabidopsis. Using quantitative real-time PCR, we show that initial P. indica colonization triggers a local, transient response of several defense-related transcripts, of which some were also induced in shoots and in distal, non-colonized roots of the same plant. Systemic effects on distal roots included the inhibition of secondary P. indica colonization. Faster and stronger induction of defense-related transcripts during secondary inoculation revealed that a P. indica pretreatment triggers root-wide priming of defense responses, which could cause the observed reduction of secondary colonization levels. Secondary P. indica colonization also induced defense responses in distant, already colonized parts of the root. Endophytic fungi therefore trigger a spatially specific response in directly colonized and in systemic root tissues of host plants.

Regenerable antioxidants-introduction of chalcogen substituents into tocopherols.

Science.gov (United States)

Poon, Jia-Fei; Singh, Vijay P; Yan, Jiajie; Engman, Lars

2015-02-02

To improve the radical-trapping capacity of the natural antioxidants, alkylthio-, alkylseleno-, and alkyltelluro groups were introduced into all vacant aromatic positions in β-, γ- and δ-tocopherol. Reaction of the tocopherols with electrophilic chalcogen reagents generated by persulfate oxidation of dialkyl dichalcogenides provided convenient but low-yielding access to many sulfur and selenium derivatives, but failed in the case of tellurium. An approach based on lithiation of the appropriate bromo-tocopherol, insertion of chalcogen into the carbon-lithium bond, air-oxidation to a dichalcogenide, and final borohydride reduction/alkylation turned out to be generally applicable to the synthesis of all chalcogen derivatives. Whereas alkylthio- and alkylseleno analogues were generally poorer quenchers of lipid peroxyl radicals than the corresponding parents, all tellurium compounds showed a substantially improved radical-trapping activity. Introduction of alkyltelluro groups into the tocopherol scaffold also caused a dramatic increase in the regenerability of the antioxidant. In a two-phase lipid peroxidation system containing N-acetylcysteine as a water-soluble co-antioxidant the inhibition time was up to six-fold higher than that recorded for the natural antioxidants. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alpha-, gamma- and delta-tocopherols reduce inflammatory angiogenesis in human microvascular endothelial cells.

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Wells, Shannon R; Jennings, Merilyn H; Rome, Courtney; Hadjivassiliou, Vicky; Papas, Konstantinos A; Alexander, Jonathon S

2010-07-01

Vitamin E, a micronutrient (comprising alpha-, beta-, gamma- and delta-tocopherols, alpha-, beta-, gamma- and delta-tocotrienols), has documented antioxidant and non-antioxidant effects, some of which inhibit inflammation and angiogenesis. We compared the abilities of alpha-, gamma- and delta-tocopherols to regulate human blood cytotoxicity (BEC) and lymphatic endothelial cytotoxicity (LEC), proliferation, invasiveness, permeability, capillary formation and suppression of TNF-alpha-induced VCAM-1 as in vitro models of inflammatory angiogenesis. alpha-, gamma- and delta-tocopherols were not toxic to either cell type up to 40 microM. In BEC, confluent cell density was decreased by all concentrations of delta- and gamma-tocopherol (10-40 microM) but not by alpha-tocopherol. LEC showed no change in cell density in response to tocopherols. delta-Tocopherol (40 microM), but not other isomers, decreased BEC invasiveness. In LEC, all doses of gamma-tocopherol, as well as the highest dose of alpha-tocopherol (40 microM), decreased cell invasiveness. delta-Tocopherol had no effect on LEC invasiveness at any molarity. delta-Tocopherol dose dependently increased cell permeability at 48 h in BEC and LEC; alpha- and gamma-tocopherols showed slight effects. Capillary tube formation was decreased by high dose (40 microM) concentrations of alpha-, gamma- and delta-tocopherol, but showed no effects with smaller doses (10-20 microM) in BEC. gamma-Tocopherol (10-20 microM) and alpha-tocopherol (10 microM), but not delta-tocopherol, increased LEC capillary tube formation. Lastly, in BEC, alpha-, gamma- and delta-tocopherol each dose-dependently reduced TNF-alpha-induced expression of VCAM-1. In LEC, there was no significant change to TNF-alpha-induced VCAM-1 expression with any concentration of alpha-, gamma- or delta-tocopherol. These data demonstrate that physiological levels (0-40 microM) of alpha-, gamma- and delta-tocopherols are nontoxic and dietary tocopherols, especially delta-tocopherol

Impact of alpha-, gamma-, and delta-tocopherol on the radiation induced oxidation of rapeseed oil triacylglycerols

Energy Technology Data Exchange (ETDEWEB)

Braunrath, Robert; Isnardy, Bettina; Solar, Sonja, E-mail: sonja.solar@univie.ac.at; Elmadfa, Ibrahim

2010-07-15

Gamma-irradiation (doses: 2, 4, 7, and 10 kGy) was used as oxidation tool to study the antioxidant effects of alpha-, gamma-, and delta-tocopherol (enrichments 500-5000 ppm) in purified rapeseed oil triacylglycerols (RSOTG). Fatty acid composition, tocopherol degradation, primary (conjugated dienes (CD) and peroxide value (POV)) and secondary (p-anisidine value) oxidation products were chosen as test parameters. Fatty acid composition did not change. While secondary oxidation products could not be found in the irradiated samples, the POVs and CDs showed a significant, dose-dependent increase. alpha-Tocopherol did not inhibit the formation of peroxides, whereas gamma- and delta-tocopherol reduced the POVs by more than 30%. No uniform effect of the different tocopherol concentrations at the particular doses could be established. The influence of the individual tocopherols on the CD formation was not pronounced. The degradation of the tocopherols decreased with increasing concentration. None of the tocopherols showed a prooxidant effect.

Impact of α-, γ-, and δ-tocopherol on the radiation induced oxidation of rapeseed oil triacylglycerols

International Nuclear Information System (INIS)

Braunrath, Robert; Isnardy, Bettina; Solar, Sonja; Elmadfa, Ibrahim

2010-01-01

Gamma-irradiation (doses: 2, 4, 7, and 10 kGy) was used as oxidation tool to study the antioxidant effects of α-, γ-, and δ-tocopherol (enrichments 500-5000 ppm) in purified rapeseed oil triacylglycerols (RSOTG). Fatty acid composition, tocopherol degradation, primary (conjugated dienes (CD) and peroxide value (POV)) and secondary (p-anisidine value) oxidation products were chosen as test parameters. Fatty acid composition did not change. While secondary oxidation products could not be found in the irradiated samples, the POVs and CDs showed a significant, dose-dependent increase. α-Tocopherol did not inhibit the formation of peroxides, whereas γ- and δ-tocopherol reduced the POVs by more than 30%. No uniform effect of the different tocopherol concentrations at the particular doses could be established. The influence of the individual tocopherols on the CD formation was not pronounced. The degradation of the tocopherols decreased with increasing concentration. None of the tocopherols showed a prooxidant effect.

Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease.

Science.gov (United States)

Mathur, Pankaj; Ding, Zufeng; Saldeen, Tom; Mehta, Jawahar L

2015-09-01

Oxidants/antioxidants play an important role in cellular homeostasis. The human body has endogenous molecules that work as antioxidants, such as glutathione, superoxide dismutase, peroxidases, and catalase. Exogenous substances in the diet, such as β-carotene, ascorbate, and vitamin E, are vital antioxidants. Of these, vitamin E is likely the most important antioxidant in the human diet, and many studies have been performed to elucidate its role in health and disease. Vitamin E is a family of several compounds, of which α-tocopherol is the most widely known analog. α-Tocopherol exhibits antioxidative property in vitro and inhibits oxidation of low-density lipoprotein cholesterol. In addition, α-tocopherol shows anti-inflammatory activity and modulates expression of proteins involved in the uptake, transport, and degradation of atherogenic lipids. Though α-tocopherol exhibits important antioxidant, anti-inflammatory, and antiatherogenic features in vitro, α-tocopherol supplements have failed to consistently reduce atherosclerosis-related events in human trials. The conflicting results have led to reconsideration of the importance previously given to α-tocopherol and led to interest in other members of vitamin E family, especially γ-tocopherol, which exerts a much more potent antioxidant, anti-inflammatory, and cardioprotective effect than α-tocopherol. This reconsideration has been backed by solid laboratory and clinical research. We suggest that the absence of γ-tocopherol in traditional preparations may be one reason for the lack of consistent salutary effects of vitamin E preparations in clinical trials. This review summarizes our current understanding of tocopherols as antioxidant molecules and emerging evidence of an important role of γ-tocopherol in the pathophysiology of atherosclerosis-related cardiovascular disease. © 2015 Wiley Periodicals, Inc.

A green multicomponent synthesis of tocopherol analogues with antiproliferative activities.

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Ingold, Mariana; Dapueto, Rosina; Victoria, Sabina; Galliusi, Germán; Batthyàny, Carlos; Bollati-Fogolín, Mariela; Tejedor, David; García-Tellado, Fernando; Padrón, José M; Porcal, Williams; López, Gloria V

2018-01-01

A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for biological tests. The evaluation of the antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr (colon) provided lead compounds with GI 50 values between 1 and 5 μM. A structure-activity relationship is also discussed. One of the studied compounds comes up as a future candidate for the development of potent tocopherol-mimetic therapeutic agents for cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Bovine milk-derived α-lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice.

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Yamaguchi, Makoto; Takai, Shoko; Hosono, Akira; Seki, Taiichiro

2014-01-01

Cyclooxygenase-2 is expressed early in colon carcinogenesis and plays crucial role in the progress of the disease. Recently, we found that α-lactalbumin had anti-inflammatory activity by inhibiting cyclooxygenase-2. In experiment 1, we investigated the effects of α-lactalbumin on the colon carcinogenesis initiated with azoxymethane (AOM) followed by promotion with dextran sodium sulfate (DSS) in mice. Dietary treatment with α-lactalbumin decreased fecal occult blood score at 3 days after DSS intake. α-Lactalbumin also decreased the colon tumor at week 9. In experiment 2, AOM-treated mice were sacrificed at 7 days after DSS intake. The plasma and colon prostaglandin E2 (PGE2) levels in AOM/DSS-treated mice were higher than those in the DSS-treated mice without initiation by AOM. α-Lactalbumin decreased PGE2 in both plasma and colon. These results suggest that α-lactalbumin effectively inhibited colon carcinogenesis, and the inhibition may be due to the decreased PGE2 by inhibiting cyclooxygenase-2 at cancer promotion stages.

Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

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Lourdes Sánchez-Sevilla

2016-10-01

Full Text Available Abstract Background The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH, by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. Methods This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC, and polyamine levels, were determined. Results Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. Conclusions Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased

A possible role of rabbit heart cytosol tocopherol binding in the transfer of tocopherol into nuclei.

OpenAIRE

Guarnieri, C; Flamigni, F; Caldarera, C M

1980-01-01

An alpha-tocopherol-binding macromolecule was isolated from the heart cytosol of rabbits fed for 1 month with an alpha-tocopherol-deficient diet. The amount of [3H]-tocopherol bound to nuclear chromatin was increased when the alpha-tocopherol-deficient heart nuclei were incubated in the presence of [3H]tocopherol-cytosol complex. In this condition, large amounts of [3H]tocopherol were associated with a subnuclear fraction that contained non-histone acidic proteins.

Tocopherol in Elder Self-Neglect

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Aung, K.; Burnett, J.; Dyer, C.; Smith, S. M.

2009-01-01

Although elder self-neglect is the most common form of elder mistreatment, its pathophysiology is not well understood. Alpha-tocopherol is a lipid soluble antioxidant required for the preservation of cell membranes. Since the association between tocopherol and cognitive impairment in older adults has been described, we explored the possibility of its role in elder self-neglect. OBJECTIVE: (1) To determine whether serum tocopherol levels are associated with elder self-neglect, and (2) to assess the association of serum tocopherol levels and cognitive function in elder self-neglect. METHODS: Serum tocopherol levels were measured in a cohort of 67 self-neglecting elders and 67 matched controls, recruited for the Consortium for Research in Elder Self-neglect of Texas. Pearson s correlation tests were performed to assess bivariate associations between serum tocopherol levels and cognitive function. RESULTS: Mean serum alpha-tocopherol levels were 10.8 +/- 4.7 ug/mL in self-neglect group and 13.0 +/- 4.9 ug/mL in control group (p = 0.006, unpaired student s t-test). None of the participants from either group had alpha-tocopherol level lower than the reference range. Mean serum gamma-tocopherol levels were 2.0 +/- 1.0 ug/mL in self-neglect group and 2.0 +/- 1.1 in control group (p=0.83). Proportion of the elders with gamma-tocopherol level lower than the reference range were 4.5% (3/66) in self-neglect group and 10.4% (7/67) in control group (p=0.32, Fisher s Exact Test). Among the self-neglecting elders, no association was found between serum alpha-tocopherol levels and the Mini-Mental State Examination (MMSE) or the Wolf-Klein Clock Drawing Test (CDT) scores (r =-0.42, p=0.75 for MMSE; r=0.08, p=0.54 for CDT). No association was found between serum gamma-tocopherol levels and the MMSE or the CDT (r=-0.12, p=0.35 for MMSE; r=0.05, p=0.68 for CDT). CONCLUSION: In our sample, neither alpha-tocopherol nor gamma-tocopherol appears to have a role in pathophysiology of elder

The naturally occurring α-tocopherol stereoisomer RRR-α-tocopherol is predominant in the human infant brain

DEFF Research Database (Denmark)

Kuchan, J M; Jensen, Søren Krogh; Johnson, E J

2016-01-01

α-Tocopherol is the principal source of vitamin E, an essential nutrient that plays a crucial role in maintaining healthy brain function. Infant formula is routinely supplemented with synthetic α-tocopherol, a racaemic mixture of eight stereoisomers with less bioactivity than the natural...... stereoisomer RRR-α-tocopherol. α-Tocopherol stereoisomer profiles have not been previously reported in the human brain. In the present study, we analysed total α-tocopherol and α-tocopherol stereoisomers in the frontal cortex (FC), hippocampus (HPC) and visual cortex (VC) of infants (n 36) who died of sudden...... infant death syndrome or other conditions. RRR-α-tocopherol was the predominant stereoisomer in all brain regions (Ptocopherol (5–17 μg/g). Mean RRR-α-tocopherol concentrations in FC, HPC and VC were 10·5, 6·8 and 5·5 μg...

Release kinetics of tocopherol and quercetin from binary antioxidant controlled-release packaging films.

Science.gov (United States)

Chen, Xi; Lee, Dong Sun; Zhu, Xuntao; Yam, Kit L

2012-04-04

This paper investigated the feasibility of manipulating packaging polymers with various degrees of hydrophobicity to release two antioxidants, tocopherol and quercetin, at rates suitable for long-term inhibition of lipid oxidation in food. For example, one antioxidant can be released at a fast rate to provide short-term/intermediate protection, whereas the other antioxidant can be released at a slower rate to provide intermediate/long-term protection of lipid oxidation. Controlled-release packaging films containing tocopherol and quercetin were produced using ethylene vinyl alcohol (EVOH), ethylene vinyl acetate (EVA), low-density polyethylene (LDPE), and polypropylene (PP) polymers; the release of these antioxidants to 95% ethanol (a fatty food simulant) was measured using UV-vis spectrophotometry, and Fickian diffusion models with appropriate initial and boundary conditions were used to fit the data. For films containing only quercetin, the results show that the release of quercetin was much faster but lasted for a much shorter time for hydrophilic polymers (EVOH and EVA) than for hydrophobic polymers (LDPE and PP). For binary antioxidant films containing tocopherol and quercetin, the results show that tocopherol released more rapidly but for a shorter period of time than quercetin in LDPE and EVOH films, and the difference is more pronounced for LDPE films than EVOH films. The results also show the presence of tocopherol can accelerate the release of quercetin. Although none of the films produced is acceptable for long-term lipid oxidation inhibition, the study provides encouraging results suggesting that acceptable films may be produced in the future using polymer blend films.

Red Wine and Pomegranate Extracts Suppress Cured Meat Promotion of Colonic Mucin-Depleted Foci in Carcinogen-Induced Rats.

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Bastide, Nadia M; Naud, Nathalie; Nassy, Gilles; Vendeuvre, Jean-Luc; Taché, Sylviane; Guéraud, Françoise; Hobbs, Ditte A; Kuhnle, Gunter G; Corpet, Denis E; Pierre, Fabrice H F

2017-01-01

Processed meat intake is carcinogenic to humans. We have shown that intake of a workshop-made cured meat with erythorbate promotes colon carcinogenesis in rats. We speculated that polyphenols could inhibit this effect by limitation of endogenous lipid peroxidation and nitrosation. Polyphenol-rich plant extracts were added to the workshop-made cured meat and given for 14 days to rats and 100 days to azoxymethane-induced rats to evaluate the inhibition of preneoplastic lesions. Colons of 100-d study were scored for precancerous lesions (mucin-depleted foci, MDF), and biochemical end points of peroxidation and nitrosation were measured in urinary and fecal samples. In comparison with cured meat-fed rats, dried red wine, pomegranate extract, α-tocopherol added at one dose to cured meat and withdrawal of erythorbate significantly decreased the number of MDF per colon (but white grape and rosemary extracts did not). This protection was associated with the full suppression of fecal excretion of nitrosyl iron, suggesting that this nitroso compound might be a promoter of carcinogenesis. At optimized concentrations, the incorporation of these plant extracts in cured meat might reduce the risk of colorectal cancer associated with processed meat consumption.

Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by alpha-tocopherol

International Nuclear Information System (INIS)

Chen, W.; Barthelman, M.; Martinez, J.; Alberts, D.; Gensler, H.L.

1997-01-01

Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis

Effect of tocopherol treatment on deterioration of edible oil quality (acid value, carbonyl value, free fatty acid and radical activity).

Science.gov (United States)

Ogata, Fumihiko; Tanaka, Yuko; Kawasaki, Naohito

2014-01-01

In this study, waste edible oil was prepared by both heat and aeration treatment, and the increasing inhibitive effect of tocopherol treatment on the acid value (AV) and carbonyl value (CV) of the oil was investigated. The AV and CV of waste edible oil treated with tocopherol were 0.1-1.0% lower than those of the nontreated oil, indicating that tocopherol exerted a radical-scavenging activity. The concentration of tocopherol decreased with time, while that of the remaining 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals increased. These results suggest that the addition of tocopherol proved to be useful for preventing the deterioration of waste edible oil.

Kynurenic acid inhibits intestinal hypermotility and xanthine oxidase activity during experimental colon obstruction in dogs.

Science.gov (United States)

Kaszaki, J; Palásthy, Z; Erczes, D; Rácz, A; Torday, C; Varga, G; Vécsei, L; Boros, M

2008-01-01

Kynurenic acid (KynA), an endogenous antagonist of N-methyl-d-aspartate (NMDA) glutamate receptors, protects the central nervous system in excitotoxic neurological diseases. We hypothesized that the inhibition of enteric glutamate receptors by KynA may influence dysmotility in the gastrointestinal tract. Group 1 of healthy dogs served as the sham-operated control, in group 2, the animals were treated with KynA, while in groups 3 and 4 mechanical colon obstruction was maintained for 7 h. Group 4 was treated with KynA at the onset of ileus. Hemodynamics and motility changes were monitored, and the activities of xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) were determined from tissue samples. Colon obstruction induced a hyperdynamic circulatory reaction, significantly elevated the motility index and increased the mucosal leucocyte accumulation and the XOR activity. The KynA treatment augmented the tone of the colon, permanently decreased the motility index of the giant colonic contractions and reduced the increases in XOR and MPO activities. These effects were concomitant with the in vitro inhibition of XOR activity. In conclusion, KynA antagonizes the obstruction-induced motility responses and XOR activation in the colon. Inhibition of enteric NMDA receptors may provide an option to influence intestinal hypermotility and inflammatory changes.

Inhibition of fungal colonization by Pseudoalteromonas tunicata provides a competitive advantage during surface colonization.

Science.gov (United States)

Franks, A; Egan, S; Holmström, C; James, S; Lappin-Scott, H; Kjelleberg, S

2006-09-01

The marine epiphytic bacterium Pseudoalteromonas tunicata produces a range of extracellular secondary metabolites that inhibit an array of common fouling organisms, including fungi. In this study, we test the hypothesis that the ability to inhibit fungi provides P. tunicata with an advantage during colonization of a surface. Studies on a transposon-generated antifungal-deficient mutant of P. tunicata, FM3, indicated that a long-chain fatty acid-coenzyme A ligase is involved in the production of a broad-range antifungal compound by P. tunicata. Flow cell experiments demonstrated that production of an antifungal compound provided P. tunicata with a competitive advantage against a marine yeast isolate during surface colonization. This compound enabled P. tunicata to disrupt an already established fungal biofilm by decreasing the number of yeast cells attached to the surface by 66% +/- 9%. For in vivo experiments, the wild-type and FM3 strains of P. tunicata were used to inoculate the surface of the green alga Ulva australis. Double-gradient denaturing gradient gel electrophoresis analysis revealed that after 48 h, the wild-type P. tunicata had outcompeted the surface-associated fungal community, whereas the antifungal-deficient mutant had no effect on the fungal community. Our data suggest that P. tunicata is an effective competitor against fungal surface communities in the marine environment.

Genetic variation of γ-tocopherol methyltransferase gene contributes to elevated α-tocopherol content in soybean seeds.

Science.gov (United States)

Dwiyanti, Maria S; Yamada, Tetsuya; Sato, Masako; Abe, Jun; Kitamura, Keisuke

2011-11-07

Improvement of α-tocopherol content is an important breeding aim to increase the nutritional value of crops. Several efforts have been conducted to improve the α-tocopherol content in soybean [Glycine max (L.) Merr.] through transgenic technology by overexpressing genes related to α-tocopherol biosynthesis or through changes to crop management practices. Varieties with high α-tocopherol content have been identified in soybean germplasms. The heritability of this trait has been characterized in a cross between high α-tocopherol variety Keszthelyi Aproszemu Sarga (KAS) and low α-tocopherol variety Ichihime. In this study, the genetic mechanism of the high α-tocopherol content trait of KAS was elucidated. Through QTL analysis and fine mapping in populations from a cross between KAS and a Japanese variety Ichihime, we identified γ-TMT3, which encodes γ-tocopherol methyltransferase, as a candidate gene responsible for high α-tocopherol concentration in KAS. Several nucleotide polymorphisms including two nonsynonymous mutations were found in the coding region of γ-TMT3 between Ichihime and KAS, but none of which was responsible for the difference in α-tocopherol concentration. Therefore, we focused on transcriptional regulation of γ-TMT3 in developing seeds and leaves. An F5 line that was heterozygous for the region containing γ-TMT3 was self-pollinated. From among the progeny, plants that were homozygous at the γ-TMT3 locus were chosen for further evaluation. The expression level of γ-TMT3 was higher both in developing seeds and leaves of plants homozygous for the γ-TMT3 allele from KAS. The higher expression level was closely correlated with high α-tocopherol content in developing seeds. We generated transgenic Arabidopsis plants harboring GUS gene under the control of γ-TMT3 promoter from KAS or Ichihime. The GUS activity assay showed that the activity of γ-TMT3 promoter from KAS was higher than that of Ichihime. The genetic variation in γ-TMT3

Genetic variation of γ-tocopherol methyltransferase gene contributes to elevated α-tocopherol content in soybean seeds

Directory of Open Access Journals (Sweden)

Abe Jun

2011-11-01

Full Text Available Abstract Background Improvement of α-tocopherol content is an important breeding aim to increase the nutritional value of crops. Several efforts have been conducted to improve the α-tocopherol content in soybean [Glycine max (L. Merr.] through transgenic technology by overexpressing genes related to α-tocopherol biosynthesis or through changes to crop management practices. Varieties with high α-tocopherol content have been identified in soybean germplasms. The heritability of this trait has been characterized in a cross between high α-tocopherol variety Keszthelyi Aproszemu Sarga (KAS and low α-tocopherol variety Ichihime. In this study, the genetic mechanism of the high α-tocopherol content trait of KAS was elucidated. Results Through QTL analysis and fine mapping in populations from a cross between KAS and a Japanese variety Ichihime, we identified γ-TMT3, which encodes γ-tocopherol methyltransferase, as a candidate gene responsible for high α-tocopherol concentration in KAS. Several nucleotide polymorphisms including two nonsynonymous mutations were found in the coding region of γ-TMT3 between Ichihime and KAS, but none of which was responsible for the difference in α-tocopherol concentration. Therefore, we focused on transcriptional regulation of γ-TMT3 in developing seeds and leaves. An F5 line that was heterozygous for the region containing γ-TMT3 was self-pollinated. From among the progeny, plants that were homozygous at the γ-TMT3 locus were chosen for further evaluation. The expression level of γ-TMT3 was higher both in developing seeds and leaves of plants homozygous for the γ-TMT3 allele from KAS. The higher expression level was closely correlated with high α-tocopherol content in developing seeds. We generated transgenic Arabidopsis plants harboring GUS gene under the control of γ-TMT3 promoter from KAS or Ichihime. The GUS activity assay showed that the activity of γ-TMT3 promoter from KAS was higher than that of

Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells.

Science.gov (United States)

Zeng, Huawei; Taussig, David P; Cheng, Wen-Hsing; Johnson, LuAnn K; Hakkak, Reza

2017-01-01

Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

21 CFR 582.5890 - Tocopherols.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tocopherols. 582.5890 Section 582.5890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5890 Tocopherols. (a) Product. Tocopherols. (b) Conditions of use. This substance is...

21 CFR 182.3890 - Tocopherols.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tocopherols. 182.3890 Section 182.3890 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Chemical Preservatives § 182.3890 Tocopherols. (a) Product. Tocopherols. (b) Conditions of use. This substance is generally recognized as safe when...

21 CFR 582.3890 - Tocopherols.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tocopherols. 582.3890 Section 582.3890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... Tocopherols. (a) Product. Tocopherols. (b) Conditions of use. This substance is generally recognized as safe...

Tocopherols in Seafood and Aquaculture Products.

Science.gov (United States)

Afonso, Cláudia; Bandarra, Narcisa M; Nunes, Leonor; Cardoso, Carlos

2016-01-01

Fish products contain various nutritionally beneficial components, namely, ω3-polyunsaturated fatty acids (ω3-PUFA), minerals, and vitamins. Particularly, tocopherols (α-, β-, γ-, and δ-tocopherol) can be provided by seafood and aquaculture products. Hence, this review shows the various aspects of tocopherols in seafood and aquaculture products. For tocopherol determination in these products, HPLC methods coupled with diode array detection in the UV area of the spectrum or fluorescence detection have been shown as sensitive and accurate. These newest methods have helped in understanding tocopherols fate upon ingestion by seafood organisms. Tocopherols pass through the intestinal mucosa mainly by the same passive diffusion mechanism as fats. After absorption, the transport mechanism is thought to consist of two loops. The first loop is dietary, including chylomicrons and fatty acids bound to carrier protein, transporting lipids mainly to the liver. The other is the transport from the liver to tissues and storage sites. Moreover, tocopherol levels in fish organisms correlate with diet levels, being adjusted in fish body depending on diet concentration. For farmed fish species, insufficient levels of tocopherols in the diet can lead to poor growth performance or to nutritional disease. The tocopherol quantity needed as a feed supplement depends on various factors, such as the vitamer mixture, the lipid level and source, the method of diet preparation, and the feed storage conditions. Other ingredients in diet may be of great importance, it has been proposed that α-tocopherol may behave as a prooxidant synergist at higher concentrations when prooxidants such as transition metals are present. However, the antioxidant action of tocopherols outweighs this prooxidant effect, provided that adequate conditions are used. In fact, muscle-based foods containing higher levels of tocopherol show, for instance, higher lipid stability. Besides, tocopherols are important not

21 CFR 182.8890 - Tocopherols.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tocopherols. 182.8890 Section 182.8890 Food and... CONSUMPTION (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients § 182.8890 Tocopherols. (a) Product. Tocopherols. (b) Conditions of use. This substance is generally recognized as safe when used in accordance...

The uptake of tocopherols by RAW 264.7 macrophages

Directory of Open Access Journals (Sweden)

Papas Andreas M

2002-10-01

Full Text Available Abstract Background Alpha-Tocopherol and gamma-tocopherol are the two major forms of vitamin E in human plasma and the primary lipid soluble antioxidants. The dietary intake of gamma-tocopherol is generally higher than that of alpha-tocopherol. However, alpha-tocopherol plasma levels are about four fold higher than those of gamma-tocopherol. Among other factors, a preferential cellular uptake of gamma-tocopherol over alpha-tocopherol could contribute to the observed higher plasma alpha-tocopherol levels. In this investigation, we studied the uptake and depletion of both alpha-tocopherol and gamma-tocopherol (separately and together in cultured RAW 264.7 macrophages. Similar studies were performed with alpha-tocopheryl quinone and gamma-tocopheryl quinone, which are oxidation products of tocopherols. Results RAW 264.7 macrophages showed a greater uptake of gamma-tocopherol compared to alpha-tocopherol (with uptake being defined as the net difference between tocopherol transported into the cells and loss due to catabolism and/or in vitro oxidation. Surprisingly, we also found that the presence of gamma-tocopherol promoted the cellular uptake of alpha-tocopherol. Mass balance considerations suggest that products other than quinone were formed during the incubation of tocopherols with macrophages. Conclusion Our data suggests that gamma-tocopherol could play a significant role in modulating intracellular antioxidant defence mechanisms. Moreover, we found the presence of gamma-tocopherol dramatically influenced the cellular accumulation of alpha-tocopherol, i.e., gamma-tocopherol promoted the accumulation of alpha-tocopherol. If these results could be extrapolated to in vivo conditions they suggest that gamma-tocopherol is selectively taken up by cells and removed from plasma more rapidly than alpha-tocopherol. This could, in part, contribute to the selective maintenance of alpha-tocopherol in plasma compared to gamma-tocopherol.

Supplementation with RRR- or all-rac-α-Tocopherol Differentially Affects the α-Tocopherol Stereoisomer Profile in the Milk and Plasma of Lactating Women.

Science.gov (United States)

Gaur, Shashank; Kuchan, Matthew J; Lai, Chron-Si; Jensen, Soren K; Sherry, Christina L

2017-07-01

Background: The naturally occurring α-tocopherol stereoisomer RRR- α-tocopherol is known to be more bioactive than synthetic α-tocopherol ( all-rac -α-tocopherol). However, the influence of this difference on the α-tocopherol stereoisomer profile of human milk is not understood. Objective: We investigated whether supplemental RRR- α-tocopherol or all-rac -α-tocopherol differentially affected the distribution of α-tocopherol stereoisomers in milk and plasma from lactating women. Methods: Eighty-nine lactating women aged 19-40 y and with a body mass index (in kg/m 2 ) ≤30 were randomly assigned at 4-6 wk postpartum to receive a daily supplement containing 45.5 mg all-rac -α-tocopherol acetate (ARAC), 22.8 mg all-rac -α-tocopherol acetate + 20.1 mg RRR -α-tocopherol (MIX), or 40.2 mg RRR- α-tocopherol (RRR). Milk and plasma were analyzed for α-tocopherol structural isomers and α-tocopherol stereoisomers at baseline and after 6 wk supplementation with the use of chiral HPLC. Results: There were no significant treatment group or time-dependent changes in milk or plasma α, γ, or δ-tocopherol. RRR- α-tocopherol was the most abundant stereoisomer in both milk and plasma in each group. Supplementation changed both milk and plasma percentage RRR- α-tocopherol (RRR > MIX > ARAC) ( P tocopherol (ARAC > MIX > RRR) ( P tocopherol increased in milk (mean ± SEM: 78% ± 2.3% compared with 82% ± 1.7%) ( P tocopherol decreased in the MIX and ARAC groups (MIX, P tocopherol stereoisomers increased (MIX, P tocopherol stereoisomers ( P tocopherol was positively correlated at baseline ( r = 0.67; P tocopherol supplementation strategy differentially affected the α-tocopherol milk and plasma stereoisomer profile in lactating women. RRR- α-tocopherol increased milk and plasma percentage RRR- α-tocopherol, whereas all-rac -α-tocopherol acetate reduced these percentages. Because RRR- α-tocopherol is the most bioactive stereoisomer, investigating the impact of

21 CFR 184.1890 - α-Tocopherols.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true α-Tocopherols. 184.1890 Section 184.1890 Food and... Substances Affirmed as GRAS § 184.1890 α-Tocopherols. (a) The α-tocopherols that are the subject of this GRAS affirmation regulation are limited to the following: (1) d-α-Tocopherol (CAS Reg. No. 59-02-9) is the chemical...

Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.

OpenAIRE

Alzamora, Rodrigo; O'Mahony, Fiona; Harvey, Brian J

2011-01-01

Excessive Cl(-) secretion is the driving force for secretory diarrhea. 17β-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17β-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17β-estradiol on cholera toxin and heat-stable enterotoxin induced Cl(-) secretion in rat colonic mucosal sheets was studied by current-voltage clamping. Selective per...

Factors Affecting Tocopherol Concentrations in Soybean Seeds.

Science.gov (United States)

Carrera, Constanza S; Seguin, Philippe

2016-12-21

Soybean seeds contain several health-beneficial compounds, including tocopherols, which are used by the nutraceutical and functional food industries. Soybean tocopherol concentrations are, however, highly variable. Large differences observed in tocopherol concentrations among soybean genotypes together with the relatively simple biosynthetic pathway involving few genes support the feasibility of selecting for high-tocopherol soybean. Tocopherol concentrations are also highly influenced by environmental factors and field management. Temperature during seed filling and soil moisture appear to be the main factors affecting tocopherol concentrations; other factors such as soil fertility and solar radiation also affect concentrations and composition. Field management decisions including seeding date, row spacing, irrigation, and fertilization also affect tocopherols. Knowledge of factors affecting soybean tocopherols is essential to develop management strategies that will lead to the production of seeds with consistent target concentrations that will meet the needs of the nutraceutical and functional food industries.

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

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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 cou...

Tocopherols in Sunflower Seedlings under Light and Dark Conditions.

Science.gov (United States)

del Moral, Lidia; Pérez-Vich, Begoña; Velasco, Leonardo

2015-01-01

The objective of this study was to evaluate the dynamics of tocopherols in cotyledons and radicles from sunflower seeds with high and low total tocopherol content, mainly in the α-tocopherol form, and from seeds with increased proportions of β-, γ-, and δ-tocopherol, both under dark and light conditions. Tocopherol content was measured every 24 h from 1 to 12 days after sowing. In all cases, the content of individual tocopherol forms in the cotyledons and radicles was reduced along the sampling period, which was more pronounced under light conditions. The presence of light had a slightly greater effect on α- and γ-tocopherol than on β- and δ-tocopherol. A marked light effect was also observed on total tocopherol content, with light promoting the reduction of tocopherol content in cotyledons and radicles. The study revealed only slight differences in the patterns of tocopherol losses in lines with different tocopherol profiles, both under dark and light conditions, which suggested that the partial replacement of α-tocopherol by other tocopherol forms had no great impact on the protection against oxidative damage in seedlings.

Tocopherol in irradiation of experimental neoplasms

International Nuclear Information System (INIS)

Kaagerud, A.; Peterson, H.-I.

1981-01-01

The influence of tocopherol, administered intramuscularly in different single doses, on the effect of local irradiation of a transplanted rat sarcoma was investigated. Tocopherol in doses of 5, 25 or 50 mg/100 g body weight enhanced significantly the tumour growth retardation induced by irradiation. Tocopherol in a dose of 100 mg/100 g body weight as a placebo preparation had no similar effect. The influence of tocopherol administered intramuscularly or orally in identical doses was similar. (Auth.)

The uptake of tocopherols by RAW 264.7 macrophages

OpenAIRE

Papas Andreas M; Huang Thomas; Stone William L; Gao Rong; Qui Min

2002-01-01

Abstract Background Alpha-Tocopherol and gamma-tocopherol are the two major forms of vitamin E in human plasma and the primary lipid soluble antioxidants. The dietary intake of gamma-tocopherol is generally higher than that of alpha-tocopherol. However, alpha-tocopherol plasma levels are about four fold higher than those of gamma-tocopherol. Among other factors, a preferential cellular uptake of gamma-tocopherol over alpha-tocopherol could contribute to the observed higher plasma alpha-tocoph...

Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.

Science.gov (United States)

Clarke, Michael W; Ward, Natalie C; Wu, Jason H Y; Hodgson, Jonathan M; Puddey, Ian B; Croft, Kevin D

2006-01-01

Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol. We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes. Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation. Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation. Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum alpha-tocopherol and

Gemifloxacin, a Fluoroquinolone Antimicrobial Drug, Inhibits Migration and Invasion of Human Colon Cancer Cells

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Jung-Yu Kan

2013-01-01

Full Text Available Gemifloxacin (GMF is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT. In addition, GMF suppresses the activation of NF-κB and cell migration and invasion induced by TNF-α and inhibits the TAK1/TAB2 interaction, resulting in decreased IκB phosphorylation and NF-κB nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.

Effects of tocopherols on oxidative stability of margarine

International Nuclear Information System (INIS)

Azizkhani, M.; Kamkar, A.; Nejad, A.S.M.

2011-01-01

Tocopherols are the most important natural antioxidants which are now added to edible oils. Each individual tocopherol (a, beta and gamma) was added to the oil phase of margarine in 0 (control), 100, 250, and 500 ppm. Anti oxidative activity was evaluated through oven test (at 60 +- 1 deg. C in 5 days and measuring peroxide value and anisidine value) and Ransimat test (110 +- 1 deg. C). Anti oxidative activity increased progressively as concentration of gamma-tocopherol increased. As the concentration of gamma-tocopherol increased from 0 to 100, and 250 ppm, oxidation of oil phase decreased. At 500 ppm, a-tocopherol acted as a prooxidant and gamma-tocopherol did not have any noticable effect, but gamma-tocopherol acted as an antioxidant. The order of anti oxidative activity of tocopherols was: a- < beta- < gamma-. (author)

miR-409-3p sensitizes colon cancer cells to oxaliplatin by inhibiting Beclin-1-mediated autophagy.

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Tan, Shifan; Shi, Huijuan; Ba, Mingchen; Lin, Shengqv; Tang, Hongsheng; Zeng, Xiaoqi; Zhang, Xiangliang

2016-04-01

The chemoresistance of colon cancer cells limits the efficacy of chemotherapy. miR-409-3p has been shown to be downregulated in various types of cancer. In the present study, we examined the role of miR-409-3p in colon cancer as well as the effects of miR‑409-3p on the sensitivity of colon cancer cells to oxaliplatin. The expression of miR-409 was significantly downregulated in the human colon cancer cell lines compared with the normal colon epithelial cells. Importantly, the miR-409-3p expression levels were lower in human colon cancer patient samples than in normal colon tissues. Moreover, we observed a negative correlation between the miR‑409-3p levels and resistance to oxaliplatin: the oxaliplatin-resistant colon cancer cells exhibited significantly downregulated miR‑409-3p levels, but higher autophagic activity than the oxaliplatin-sensitive cells. Using bioinformatics analysis, we predicted that miR‑409-3p miRNA binds to the key autophagy gene encoding Beclin-1. Our findings indicated that the overexpression of miR‑409-3p inhibited Beclin-1 expression and autophagic activity by binding to the 3'-untranslated region of Beclin-1 mRNA. In addition, the overexpression of miR‑409-3p enhanced the chemosensitivity of the oxaliplatin-sensitive and oxaliplatin-resistant colon cancer cells. The restoration of Beclin-1 abrogated these effects of miR‑409-3p. In a xenograft model using nude mice, we examined the effects of miR‑409-3p on tumor growth during chemotherapy. miR‑409-3p overexpression sensitized the tumor to chemotherapy, while inhibiting chemotherapy-induced autophagy in a manner dependent on Beclin-1. The findings of our study suggest that miR-409-3p is capable of enhancing the chemosensitivity of colon cancer cells by inhibiting Beclin-1-mediated autophagy.

microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2.

Science.gov (United States)

Nie, Jing; Liu, Lin; Zheng, Wei; Chen, Lin; Wu, Xin; Xu, Yingxin; Du, Xiaohui; Han, Weidong

2012-01-01

Deregulated microRNAs participate in carcinogenesis and cancer progression, but their roles in cancer development remain unclear. In this study, miR-365 expression was found to be downregulated in human colon cancer tissues as compared with that in matched non-neoplastic mucosa tissues, and its downregulation was correlated with cancer progression and poor survival in colon cancer patients. Functional studies revealed that restoration of miR-365 expression inhibited cell cycle progression, promoted 5-fluorouracil-induced apoptosis and repressed tumorigenicity in colon cancer cell lines. Furthermore, bioinformatic prediction and experimental validation were used to identify miR-365 target genes and indicated that the antitumor effects of miR-365 were probably mediated by its targeting and repression of Cyclin D1 and Bcl-2 expression, thus inhibiting cell cycle progression and promoting apoptosis. These results suggest that downregulation of miR-365 in colon cancer may have potential applications in prognosis prediction and gene therapy in colon cancer patients.

Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

LENUS (Irish Health Repository)

Hogan, A M

2012-02-01

BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.

Nascent VLDL from liver perfusions of cynomolgus monkeys are preferentially enriched in RRR- compared with SRR-alpha-tocopherol: Studies using deuterated tocopherols

International Nuclear Information System (INIS)

Traber, M.G.; Rudel, L.L.; Burton, G.W.; Hughes, L.; Ingold, K.U.; Kayden, H.J.

1990-01-01

The transport and secretion of vitamin E in lipoproteins have been studied in cynomolgus monkeys fed tocopherols labeled with different amounts of deuterium. The animals were fed a single dose of vitamin E containing 60 mumol of each 2R,4'R,8'R-alpha-(5,7-(C2H3)2)tocopheryl acetate (d6-RRR-alpha-tocopheryl acetate; alpha-tocopherol with natural stereochemistry), 2S,4'R,8'R-alpha-5-(C2H3)tocopheryl acetate (d3-SRR-alpha-tocopheryl acetate; alpha-tocopherol with unnatural stereochemistry), and 2R,4'R,8'R-gamma-(3,4-2H)tocopherol (d2-RRR-gamma-tocopherol; gamma-tocopherol with natural stereochemistry). Chylomicrons, as well as the other plasma lipoproteins, contained equal concentrations of all three tocopherols at the earliest time points after feeding suggesting that all three tocopherols were absorbed equally. At later times plasma lipoproteins became preferentially enriched in d6-RRR-alpha-tocopherol. This is likely to be due to hepatic secretion of VLDL (very low density lipoproteins) and other lipoproteins, which were enriched in d6-RRR-alpha-tocopherol, as demonstrated in the lipoproteins isolated from perfused livers that had been obtained 24 h following the administration of the deuterated tocopherols. Taken together these data demonstrate that the liver, not the intestine, is the likely site of discrimination between tocopherol isomers and that the liver secretes nascent lipoproteins preferentially enriched in d6-RRR-alpha-tocopherol

Development of sunflower germplasm with high delta-tocopherol content

OpenAIRE

Velasco L.; Pérez-Vich B.; Fernández-Martínez J.M.

2004-01-01

Tocopherols are the main compounds with antioxidant activity in oilseeds Sunflower seeds contain predominantly alpha-tocopherol, which accounts for more than 90% of the total tocopherols in the seeds. This tocopherol derivative possesses a maximum vitamin E or in vivo antioxidant activity, but it exerts a minimum in vitro protective action in oils and food containing them. Other tocopherol derivatives such as beta-, gamma-, and delta-tocopherol are more powerful antioxidants than alpha-tocoph...

Some rape/canola seed oils: fatty acid composition and tocopherols.

Science.gov (United States)

Matthaus, Bertrand; Özcan, Mehmet Musa; Al Juhaimi, Fahad

2016-03-01

Seed samples of some rape and canola cultivars were analysed for oil content, fatty acid and tocopherol profiles. Gas liquid chromotography and high performance liquid chromotography were used for fatty acid and tocopherol analysis, respectively. The oil contents of rape and canola seeds varied between 30.6% and 48.3% of the dry weight (ptocopherols were found in rape and canola oils in various amounts: α-tocopherol, γ-tocopherol, δ-tocopherol, β-tocopherol and α-tocotrienol. The major tocopherol in the seed oils of rape and canola cultivars were α-tocopherol (13.22-40.01%) and γ-tocopherol (33.64-51.53%) accompanied by α-T3 (0.0-1.34%) and δ-tocopherol (0.25-1.86%) (ptocopherol contents differ significantly among the cultivars.

Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats

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Takagi Tomohisa

2012-09-01

Full Text Available Abstract Background The pathogenesis of inflammatory bowel disease (IBD is complex, and an effective therapeutic strategy has yet to be established. Recently, carbon monoxide (CO has been reported to be capable of reducing inflammation by multiple mechanisms. In this study, we evaluated the role of colonic CO insufflation in acute colitis induced by trinitrobenzene sulfonic acid (TNBS in rats. Methods Acute colitis was induced with TNBS in male Wistar rats. Following TNBS administration, the animals were treated daily with 200 ppm of intrarectal CO gas. The distal colon was removed to evaluate various parameters of inflammation, including thiobarbituric acid (TBA-reactive substances, tissue-associated myeloperoxidase (MPO activity, and the expression of cytokine-induced neutrophil chemoattractant (CINC-1 in colonic mucosa 7 days after TNBS administration. Results The administration of TNBS induced ulceration with surrounding edematous swelling in the colon. In rats treated with CO gas, the colonic ulcer area was smaller than that of air-treated rats 7 days after TNBS administration. The wet colon weight was significantly increased in the TNBS-induced colitis group, which was markedly abrogated by colonic insufflation with CO gas. The increase of MPO activity, TBA-reactive substances, and CINC-1 expression in colonic mucosa were also significantly inhibited by colonic insufflation with CO gas. Conclusions Colonic insufflation with CO gas significantly ameliorated TNBS-induced colitis in rats. Clinical application of CO gas to improve colonic inflammatory conditions such as IBD might be useful.

Modulated phases of phospholipid bilayers induced by tocopherols.

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Kamal, Md Arif; Raghunathan, V A

2012-11-01

The influence of α-, γ- and δ-tocopherols on the structure and phase behavior of dipalmitoyl phosphatidylcholine (DPPC) bilayers has been determined from X-ray diffraction studies on oriented multilayers. In all the three cases the main-transition temperature (T(m)) of DPPC was found to decrease with increasing tocopherol concentration up to around 25 mol%. Beyond this the main transition is suppressed in the case of γ-tocopherol, whereas T(m) becomes insensitive to composition in the other two cases. The pre-transition is found to be suppressed over a narrow tocopherol concentration range between 7.5 and 10 mol% in DPPC-γ-tocopherol and DPPC-δ-tocopherol bilayers, and the ripple phase occurs down to the lowest temperature studied. In all the three cases a modulated phase is observed above a tocopherol concentration of about 10 mol%, which is similar to the P(β) phase reported in DPPC-cholesterol bilayers. This phase is found to occur even in excess water conditions at lower tocopherol concentrations, and consists of bilayers with periodic height modulation. These results indicate the ability of tocopherols to induce local curvature in membranes, which could be important for some of their biological functions. Copyright © 2012 Elsevier B.V. All rights reserved.

Expression of modified tocopherol content and profile in sunflower tissues.

Science.gov (United States)

Del Moral, Lidia; Fernández-Martínez, José M; Pérez-Vich, Begoña; Velasco, Leonardo

2012-01-30

Alpha-tocopherol is the predominant tocopherol form in sunflower seeds. Sunflower lines that accumulate increased levels of beta-, gamma- and delta-tocopherol in seeds as well as lines with reduced and increased total seed tocopherol content have been developed. The objective of this research was to evaluate whether the modified tocopherol levels are expressed in plant tissues other than seeds. Lines with increased levels of beta-, gamma- and delta-tocopherol in seeds also possessed increased levels of these tocopherols in leaves, roots and pollen. Correlation coefficients for the proportion of individual tocopherols in different plant tissues were significantly positive in all cases, ranging from 0.68 to 0.97. A line with reduced tocopherol content in seeds also showed reduced content in roots and pollen. Genetic modifications producing altered seed tocopherol profiles in sunflower are also expressed in leaves, roots and pollen. Reduced total seed tocopherol content is mainly expressed at the root and pollen level. The expression of tocopherol mutations in other plant tissues will enable further studies on the physiological role of tocopherols and could be of interest for early selection for these traits in breeding programmes. Copyright © 2011 Society of Chemical Industry.

Serum α-tocopherol and γ-tocopherol concentrations and prostate cancer risk in the PLCO Screening Trial: a nested case-control study.

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Stephanie J Weinstein

Full Text Available BACKGROUND: Vitamin E compounds exhibit prostate cancer preventive properties experimentally, but serologic investigations of tocopherols, and randomized controlled trials of supplementation in particular, have been inconsistent. Many studies suggest protective effects among smokers and for aggressive prostate cancer, however. METHODS: We conducted a nested case-control study of serum α-tocopherol and γ-tocopherol and prostate cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, with 680 prostate cancer cases and 824 frequency-matched controls. Multivariate-adjusted, conditional logistic regression models were used to estimate odds ratios (OR and 95% confidence intervals (CIs for tocopherol quintiles. RESULTS: Serum α-tocopherol and γ-tocopherol were inversely correlated (r = -0.24, p<0.0001. Higher serum α-tocopherol was associated with significantly lower prostate cancer risk (OR for the highest vs. lowest quintile = 0.63, 95% CI 0.44-0.92, p-trend 0.05. By contrast, risk was non-significantly elevated among men with higher γ-tocopherol concentrations (OR for the highest vs. lowest quintile = 1.35, 95% CI 0.92-1.97, p-trend 0.41. The inverse association between prostate cancer and α-tocopherol was restricted to current and recently former smokers, but was only slightly stronger for aggressive disease. By contrast, the increased risk for higher γ-tocopherol was more pronounced for less aggressive cancers. CONCLUSIONS: Our findings indicate higher α-tocopherol status is associated with decreased risk of developing prostate cancer, particularly among smokers. Although two recent controlled trials did not substantiate an earlier finding of lower prostate cancer incidence and mortality in response to supplementation with a relatively low dose of α-tocopherol, higher α-tocopherol status may be beneficial with respect to prostate cancer risk among smokers. Determining what stage of prostate cancer

Conjugated linoleic acid influences the metabolism of tocopherol in lactating rats but has little effect on tissue tocopherol concentrations in pups.

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Zeitz, Johanna O; Most, Erika; Eder, Klaus

2016-05-31

Conjugated linoleic acid (CLA) is known to affect the lipid metabolism in growing and lactating animals. However, potential effects on the metabolism of fat-soluble vitamins in lactating animals and co-occurring effects on their offspring are unknown. We aimed to investigate the effects of dietary CLA on concentrations of tocopherol in various tissues of lactating rats and their offspring and expression of genes involved in tocopherol metabolism. Twenty-eight Wistar Han rats were allocated to 2 groups and fed either a control diet (control group) or a diet containing 0.9 % of cis-9, trans-11 and trans-10, cis-12 (1:1) CLA (CLA group) during pregnancy and lactation. Feed intake of dams and body weight of dams and their pups were recorded weekly. Tocopherol concentrations in various body tissues were determined at day 14 of lactation in dams and 1, 7 and 14 days after birth in pups. Expression of selected genes involved in metabolism of tocopherol was determined in dams and pups. The data were statistically analysed by analysis of variance. Feed intake and body weight development of nursing rats and their pups was similar in both groups. In livers of CLA-fed dams, tocopherol concentrations decreased by 24 % but expression of TTPA and CYP3A1, involved in tocopherol transport and metabolism, were not influenced. In the dams' adipose tissue, gene expression of receptors involved in tissue tocopherol uptake, LDLR and SCARB1, but not of LPL, increased by 30 to 50 % and tocopherol concentrations increased by 47 % in CLA-fed compared to control dams. Expression of LPL, LDLR and SCARB1 in mammary gland was not influenced by CLA-feeding. Tocopherol concentrations in the pup's livers and lungs were similar in both groups, but at 14 days of age, adipose tissue tocopherol concentrations, and LDLR and SCARB1 expression, were higher in the CLA-exposed pups. We show that dietary CLA affects tissue concentrations of tocopherol in lactating rats and tocopherol metabolism in

Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer.

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Yang, Fei; Gao, Jun-Yi; Chen, Hua; Du, Zhen-Hua; Zhang, Xue-Qun; Gao, Wei

2017-01-01

Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim) were also detected. We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 μM) and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim. Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer.

21 CFR 182.8892 - α-Tocopherol acetate.

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2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true α-Tocopherol acetate. 182.8892 Section 182.8892 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD...-Tocopherol acetate. (a) Product. α-Tocopherol acetate. (b) Conditions of use. This substance is generally...

21 CFR 582.5892 - a-Tocopherol acetate.

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2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false a-Tocopherol acetate. 582.5892 Section 582.5892 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5892 a-Tocopherol acetate. (a) Product. a-Tocopherol acetate. (b) Conditions of use. This...

Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

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Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan

2009-01-01

ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

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Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

2013-01-01

The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

Transfer and targeted overexpression of γ-tocopherol methyltransferase (γ-TMT) gene using seed-specific promoter improves tocopherol composition in Indian soybean cultivars.

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Arun, Muthukrishnan; Subramanyam, Kondeti; Theboral, Jeevaraj; Sivanandhan, Ganeshan; Rajesh, Manoharan; Kapil Dev, Gnanajothi; Jaganath, Balusamy; Manickavasagam, Markandan; Girija, Shanmugam; Ganapathi, Andy

2014-02-01

Soybean oil contains high levels of tocopherols which are an important source of vitamin E in human diet. The conversion of γ- to α-tocopherol catalyzed by γ-tocopherol methyltransferase (γ-TMT) is found to be the rate limiting factor in soybean which influences the tocopherol composition. Using Agrobacterium-mediated transformation, we overexpressed the γ-TMT gene of Perilla frutescens under the control of the seed-specific promoter vicillin in cultivar Pusa 16. Transgene integration and expression was confirmed in five independently transformed GUS positive soybean plants by polymerase chain reaction (PCR), Southern hybridization, and reverse transcriptase-PCR (RT-PCR). High-performance liquid chromatography (HPLC) analysis showed that overexpression of Pf-γ-TMT resulted in efficient conversion of γ-tocopherol to α-tocopherol and concomitant increase in seed α-tocopherol content in RT-PCR positive plants. The protocol was successfully applied to three more cultivars PK 416, Gujarat soybean 1, and VL soya 1 in which seeds of transformed plants showed elevated level of α-tocopherol than wild-type seeds.

Molecular characterization of tocopherol biosynthetic genes in sweetpotato that respond to stress and activate the tocopherol production in tobacco.

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Ji, Chang Yoon; Kim, Yun-Hee; Kim, Ho Soo; Ke, Qingbo; Kim, Gun-Woo; Park, Sung-Chul; Lee, Haeng-Soon; Jeong, Jae Cheol; Kwak, Sang-Soo

2016-09-01

Tocopherol (vitamin E) is a chloroplast lipid that is presumed to be involved in the plant response to oxidative stress. In this study, we isolated and characterized five tocopherol biosynthetic genes from sweetpotato (Ipomoea batatas [L.] Lam) plants, including genes encoding 4-hydroxyphenylpyruvate dioxygenase (IbHPPD), homogentisate phytyltransferase (IbHPT), 2-methyl-6-phytylbenzoquinol methyltransferase (IbMPBQ MT), tocopherol cyclase (IbTC) and γ-tocopherol methyltransferase (IbTMT). Fluorescence microscope analysis indicated that four proteins localized into the chloroplast, whereas IbHPPD observed in the nuclear. Quantitative RT-PCR analysis revealed that the expression patterns of the five tocopherol biosynthetic genes varied in different plant tissues and under different stress conditions. All five genes were highly expressed in leaf tissues, whereas IbHPPD and IbHPT were highly expressed in the thick roots. The expression patterns of these five genes significantly differed in response to PEG, NaCl and H2O2-mediated oxidative stress. IbHPPD was strongly induced following PEG and H2O2 treatment and IbHPT was strongly induced following PEG treatment, whereas IbMPBQ MT and IbTC were highly expressed following NaCl treatment. Upon infection of the bacterial pathogen Pectobacterium chrysanthemi, the expression of IbHPPD increased sharply in sweetpotato leaves, whereas the expression of the other genes was reduced or unchanged. Additionally, transient expression of the five tocopherol biosynthetic genes in tobacco (Nicotiana bentamiana) leaves resulted in increased transcript levels of the transgenes expressions and tocopherol production. Therefore, our results suggested that the five tocopherol biosynthetic genes of sweetpotato play roles in the stress defense response as transcriptional regulators of the tocopherol production. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Inhibition of phospholipaseD2 increases hypoxia-induced human colon cancer cell apoptosis through inactivating of the PI3K/AKT signaling pathway.

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Liu, Maoxi; Fu, Zhongxue; Wu, Xingye; Du, Kunli; Zhang, Shouru; Zeng, Li

2016-05-01

Hypoxia is a common feature of solid tumor, and is a direct stress that triggers apoptosis in many human cell types. As one of solid cancer, hypoxia exists in the whole course of colon cancer occurrence and progression. Our previous studies shown that hypoxia induce high expression of phospholipase D2 (PLD2) and survivin in colon cancer cells. However, the correlation between PLD2 and survivin in hypoxic colon cancer cells remains unknown. In this study, we observed significantly elevated PLD2 and survivin expression levels in colon cancer tissues and cells. This is a positive correlation between of them, and co-expression of PLD2 and survivin has a positive correlation with the clinicpatholic features including tumor size, TNM stage, and lymph node metastasis. We also found that hypoxia induced the activity of PLD increased significant mainly caused by PLD2 in colon cancer cells. However, inhibition the activity of PLD2 induced by hypoxia promotes the apoptosis of human colon cancer cells, as well as decreased the expression of apoptosis markers including survivin and bcl2. Moreover, the pharmacological inhibition of PI3K/AKT supported the hypothesis that promotes the apoptosis of hypoxic colon cancer cells by PLD2 activity inhibition may through inactivation of the PI3K/AKT signaling pathway. Furthermore, interference the PLD2 gene expression leaded to the apoptosis of hypoxic colon cancer cells increased and also decreased the expression level of survivin and bcl2 may through inactivation of PI3K/AKT signaling pathway. These results indicated that PLD2 play antiapoptotic role in colon cancer under hypoxic conditions, inhibition of the activity, or interference of PLD2 gene expression will benefit for the treatment of colon cancer patients.

Inhibitory effects of tocopherols on expression of the cyclooxygenase-2 gene in RAW264.7 cells stimulated by lipopolysaccharide, tumor necrosis factor-α or Porphyromonas gingivalis fimbriae.

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Murakami, Yukio; Kawata, Akifumi; Koh, Teho; Seki, Yuya; Tamura, Seiko; Katayama, Tadashi; Fujisawa, Seiichiro

2013-01-01

Tocopherols, which include α-, β-, γ-, and δ-tocopherol, protect cells against harmful free radicals and play an important role in preventing many human diseases such as cancer, inflammatory disorders, and ageing itself. However, the causal relationships between periodontal or oral chronic diseases and tocopherols have not been sufficiently studied. The present study investigated the inhibitory effects of these compounds on the expression of cyclooxygenase-2 (COX2) mRNA in RAW264.7 cells stimulated with lipopolysaccharide (LPS), tumor necrosis factor-α (TNFα) or fimbriae of Poryphyromonas gingivalis (Pg), an oral anaerobe. The cytotoxicity (EC₅₀) of tocopherols toward RAW cells was determined using a cell counting kit (CCK-8). The regulatory effect of these compounds on the expression of COX2 mRNA stimulated with LPS, TNFα or Pg fimbriae was investigated using real-time polymerase chain reaction (PCR). Each tocopherol had similarly low cytotoxicity. COX2 gene expression in RAW cells after exposure to the three different macrophage activators was inhibited by the tocopherols (ptocopherol, β-, γ- and δ-tocopherol exhibited greater inhibitory effects (pTocopherols exhibit anti-inflammatory activity, and β-, γ- and δ-tocopherol have particularly more potent anti-inflammatory activity than α-tocopherol. Tocopherols may have potential utility for prevention of periodontal and chronic oral diseases.

Targeting tumor multicellular aggregation through IGPR-1 inhibits colon cancer growth and improves chemotherapy.

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Woolf, N; Pearson, B E; Bondzie, P A; Meyer, R D; Lavaei, M; Belkina, A C; Chitalia, V; Rahimi, N

2017-09-18

Adhesion to extracellular matrix (ECM) is crucially important for survival of normal epithelial cells as detachment from ECM triggers specific apoptosis known as anoikis. As tumor cells lose the requirement for anchorage to ECM, they rely on cell-cell adhesion 'multicellular aggregation' for survival. Multicellular aggregation of tumor cells also significantly determines the sensitivity of tumor cells to the cytotoxic effects of chemotherapeutics. In this report, we demonstrate that expression of immunoglobulin containing and proline-rich receptor-1 (IGPR-1) is upregulated in human primary colon cancer. Our study demonstrates that IGPR-1 promotes tumor multicellular aggregation, and interfering with its adhesive function inhibits multicellular aggregation and, increases cell death. IGPR-1 supports colon carcinoma tumor xenograft growth in mouse, and inhibiting its activity by shRNA or blocking antibody inhibits tumor growth. More importantly, IGPR-1 regulates sensitivity of tumor cells to the chemotherapeutic agent, doxorubicin/adriamycin by a mechanism that involves doxorubicin-induced AKT activation and phosphorylation of IGPR-1 at Ser220. Our findings offer novel insight into IGPR-1's role in colorectal tumor growth, tumor chemosensitivity, and as a possible novel anti-cancer target.

Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer

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Yang F

2017-09-01

Full Text Available Fei Yang,1,* Jun-Yi Gao,2,* Hua Chen,1 Zhen-Hua Du,1 Xue-Qun Zhang,3 Wei Gao4 1Department of Pathology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 2Department of Clinical Medicine, Weifang Medical College, Weifang, 3Graduate School, Taishan Medical University, Xintai, 4Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. Methods: In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim were also detected. Results: We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 µM and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim. Conclusion: Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer. Keywords: human colon cancer, PI3K/Akt/mTOR pathway, BEZ235, PI3KCA knockdown

Tocopherol levels in different mango varieties correlate with MiHPPD expression and its over-expression elevates tocopherols in transgenic Arabidopsis and tomato.

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Singh, Rajesh K; Chaurasia, Akhilesh K; Bari, Rupesh; Sane, Vidhu A

2017-10-01

Mango fruit tocopherol levels vary in different varieties during ripening. This study shows that tocopherol accumulation is highly correlated with its p-hydroxyphenyl pyruvate dioxygenase ( MiHPPD ) gene expression during ripening. MiHPPD transcript is ethylene induced and differentially expressed in four mango varieties used in this study. Higher/lower accumulation of tocopherol (mainly α-tocopherol) was achieved by heterologous expression of MiHPPD in Arabidopsis and tomato. The results suggest that tocopherol accumulation in mango fruit is correlated to MiHPPD gene expression. Over-expression of MiHPPD gene channelizes the flux towards tocophreol biosynthesis and could be used as a potential tool for metabolic engineering.

Tocopherol composition of deodorization distillates and their antioxidative activity.

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Nogala-Kalucka, Malgorzata; Korczak, Jozef; Wagner, Karl-Heinz; Elmadfa, Ibrahim

2004-02-01

During the last stage of plant oil refining, deodorization distillates containing very important biological substances such as tocopherols, sterols, terpenoids or hydrocarbons are formed as a by-products. This study aimed at evaluating the content and antioxidant capacity of tocopherol concentrates from deodorization distillates obtained after the refining of rapeseed, soybean and sunflower oil. The majority of the matrix substances were eliminated from deodorization distillates by freezing with an acetone solution at -70 degrees C. The tocopherol concentrates obtained in this way contained approximately fivefold more tocopherols than the quantity in condensates after deodorization. Antioxidant activity was investigated by observing the peroxide value at 25 degrees C and using the Oxidograph test. The test medium was lard enriched with the tocopherol concentrates of the three plant oils versus single, synthetic alpha-, gamma- and delta-tocopherols (-T), which served for comparison. In these model systems, all investigated tocopherol concentrates exhibited antioxidant capacity. Their antioxidant effect was significantly lower than that of single delta-T and gamma-T, but significantly higher than alpha-T. The results prove that natural tocopherol concentrates obtained from plant oils are valuable food antioxidants and they also increase the biological and nutritional value of food especially when administered to animal fats or food of animal origin. Tocopherol concentrates can fully replace synthetic antioxidants that have been used thus far.

Disintegration and dimerization of δ-tocopherol under radiation effect

International Nuclear Information System (INIS)

Jasinska-Stepniak, A.; Gogolewski, M.; Zabielski, J.

1996-01-01

The goal of the work was to recognize scala changes of δ-tocopherol in model system (diluted in benzene, ethanol and ''in substantia'') after 2.5, 5, 10 and 20 kGy dose irradiation. δ-tocopherol and its mild oxidation products (dimers) after TLC separation were quantitatively determined with Emmerie-Engel method. Relations dose-effect have been defined and radiation capacity has been calculated. The results show that disintegration of δ-tocopherol diluted in ethanol is about ten times stronger the diluted in benzene. δ-tocopherol in benzene was dimerized. The most stable after irradiation was δ-tocopherol ''in substantia''. (author)

Inhibition effect of Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis and their related products on human colonic smooth muscle in vitro.

Directory of Open Access Journals (Sweden)

Jing Gong

Full Text Available To investigate the effects of four strains, generally used in clinic, including Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis, and their related products on human colonic smooth muscle in vitro.Human colonic circular muscle strips obtained from disease-free margins of resected segments from 25 patients with colorectal cancer were isometrically examined in a constant-temperature organ bath and exposed to different concentrations of living bacteria, sonicated cell fractions and cell-free supernatant (CFS. The area under the curve (AUC representing the contractility of smooth muscle strips was calculated.(1 The four living probiotics inhibited the contractility of human colonic muscle strips only at high concentration (1010 CFUs/mL, all P0.05.Four common probiotics related products, including the sonicated cell fractions and the CFS, obviously inhibited human colonic smooth muscles strips contraction in a dose-dependent manner. Only high concentration living probiotics (1010 CFUs/mL can inhibit the colonic smooth muscles strips contraction. The NO pathway may be partly involved in the inhibitory effect of CFS from Streptococcus thermophilus and Enterococcus faecalis.

Tocopherols in rose hips (Rosa spp.) during ripening.

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Andersson, Staffan C; Olsson, Marie E; Gustavsson, Karl-Erik; Johansson, Eva; Rumpunen, Kimmo

2012-08-15

Rose hips are used as a food ingredient and in health products. They are rich in various bioactive compounds such as carotenoids and vitamin C, but data on their vitamin E content (tocopherols and tocotrienols) are limited. In this study, four different species of Rosa were analysed for tocopherol and tocotrienol content during ripening in three different years. Only α- and γ-tocopherol were found in the fleshy parts of the rose hips, and the tocopherol content and vitamin E activity varied depending on date of harvesting, species and year. The amount of vitamin E activity differed between species of Rosa and years, whereas the changes during ripening were relatively small. The choice of species must be considered if tocopherol content is to be optimised when rose hips are used as a food ingredient. Copyright © 2012 Society of Chemical Industry.

Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity

International Nuclear Information System (INIS)

Qi, Wentao; Weber, Christopher R; Wasland, Kaarin; Savkovic, Suzana D

2011-01-01

Soy consumption is associated with a lower incidence of colon cancer which is believed to be mediated by one of its of components, genistein. Genistein may inhibit cancer progression by inducing apoptosis or inhibiting proliferation, but mechanisms are not well understood. Epidermal growth factor (EGF)-induced proliferation of colon cancer cells plays an important role in colon cancer progression and is mediated by loss of tumor suppressor FOXO3 activity. The aim of this study was to assess if genistein exerts anti-proliferative properties by attenuating the negative effect of EGF on FOXO3 activity. The effect of genistein on proliferation stimulated by EGF-mediated loss of FOXO3 was examined in human colonic cancer HT-29 cells. EGF-induced FOXO3 phosphorylation and translocation were assessed in the presence of genistein. EGF-mediated loss of FOXO3 interactions with p53 (co-immunoprecipitation) and promoter of p27kip1 (ChIP assay) were examined in presence of genistein in cells with mutated p53 (HT-29) and wild type p53 (HCT116). Silencing of p53 determined activity of FOXO3 when it is bound to p53. Genistein inhibited EGF-induced proliferation, while favoring dephosphorylation and nuclear retention of FOXO3 (active state) in colon cancer cells. Upstream of FOXO3, genistein acts via the PI3K/Akt pathway to inhibit EGF-stimulated FOXO3 phosphorylation (i.e. favors active state). Downstream, EGF-induced disassociation of FOXO3 from mutated tumor suppressor p53, but not wild type p53, is inhibited by genistein favoring FOXO3-p53(mut) interactions with the promoter of the cell cycle inhibitor p27kip1 in colon cancer cells. Thus, the FOXO3-p53(mut) complex leads to elevated p27kip1 expression and promotes cell cycle arrest. These novel anti-proliferative mechanisms of genistein suggest a possible role of combining genistein with other chemoreceptive agents for the treatment of colon cancer

Expression and inhibition of matrix metalloproteinase (MMP)-8, MMP-9 and MMP-12 in early colonic anastomotic repair

DEFF Research Database (Denmark)

Krarup, Peter-Martin; Eld, Mikkel; Heinemeier, Katja

2013-01-01

of specific MMPs responsible for the weakening of anastomoses can be used to optimise MMP inhibition therapy. We aimed to quantify transcript and protein levels of multiple MMPs in colonic anastomoses and evaluate the effect of inhibiting the MMPs that displayed the highest expression levels on anastomotic...

Antioxidant properties of mushroom mycelia obtained by batch cultivation and tocopherol content affected by extraction procedures.

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Vamanu, Emanuel

2014-01-01

The determination of the antioxidant potential of lyophilized mushroom mycelia from 5 strains of the species Pleurotus ostreatus and Coprinus comatus (obtained by submerged cultivation in batch system) was analyzed as ethanolic extracts by evaluating ABTS and the hydroxyl scavenging activity, FRAP method, the chelating capacity, the inhibition of human erythrocyte hemolysis, and the inhibition of xanthine oxidase activity. The main compounds present in all extracts were determined by HPLC chromatography. Overall, results demonstrated that the biologically active substances content is modulated by the extraction method used. The most beneficial extract, characterized by determining the EC50 value, was that of C. comatus M8102, followed by P. ostreatus PQMZ91109. Significant amount of α-tocopherol (179.51 ± 1.51 mg/100 g extract) was determined as well as flavones such as rutin and apigenin. In the P. ostreatus PQMZ91109 extract, 4.8 ± 0.05 mg/100 g extract of tocopherol acetate known to play a significant role as an antioxidant in skin protection against oxidative stress generated by UV rays was determined. The various correlations (r (2) = 0.7665-0.9426 for tocopherol content) assessed and the composition of extracts in fluidized bed from the mycelia of the tested species depicted a significant pharmacological potential as well as the possibility of usage in the development of new functional products.

Ethanolic Extract of Traditional Chinese Medicine (TCM) Gamboge Inhibits Colon Cancer via the Wnt/Beta-Catenin Signaling Pathway in an Orthotopic Mouse Model.

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Wang, Wei; Li, Youran; Chen, Yiqi; Chen, Hongjin; Zhu, Ping; Xu, Minmin; Wang, Hao; Wu, Minna; Yang, Zhijian; Hoffman, Robert M; Gu, Yunfei

2018-04-01

The aim of the present study was to investigate the efficacy of an ethanolic extract of gamboge (EEG), a traditional Chinese medicine (TCM), both in vitro on colon cancer cells and in vivo in an orthotopic mouse model of human colon cancer. The in vitro cytotoxicity of EEG on colon cancer cells was determined with the CCK8 proliferation assay and the Annexin V-PE/7-AAD apoptosis assay. Efficacy of EEG in vivo was evaluated in an orthotopic mouse model of human colon cancer implated with the green fluorescent protein-expressing human colon cancer cell line SW480-GFP. The tumor-bearing mice were treated with vehicle (0.2 ml/dose normal saline, po, daily), irinotecan (50 mg/kg/dose, ip, twice a week), 5-FU (15 mg/kg/dose, ip, every other day) as positive controls or EEG at doses of 12.5, 25 and 50 mg/kg/dose, po, daily. Real-time fluorescence imaging was performed to determine tumor inhibition in each treated group compared to the untreated controls. The protein expression of β-catenin, MMP-7, cyclin D1 and E-cadherin in the tumors was analyzed by immunohistochemistry. EEG significantly induced proliferation inhibition and apoptosis of SW480 colon cancer cells in vitro in a dose-dependent manner. Tumor growth in the colon-cancer orthotopic model was significantly inhibited by irinotecan, 5-FU and all three doses of EEG. The efficacy of EEG was comparable to irinotecan and 5-FU. Irinotecan, 5-FU and 50 mg/kg EEG significantly decreased the protein expression of β-catenin and MMP-7. Cyclin D1 expression was decreased and E-cadherin expression was increased by irinotecan, 5-FU and all three doses of EEG. The present study demonstrates anti-tumor efficacy of EEG on colon cancer both in vitro and in vivo through inducing proliferation inhibition and apoptosis of SW480 colon cancer cells and inhibiting tumor growth, respectively. EEG exerts anti-tumor activity at least partly via down-regulation of the Wnt/β-catenin signaling pathway. Copyright© 2018, International

Dietary pectin and calcium inhibit colonic proliferation in vivo by differing mechanisms.

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Umar, S; Morris, A P; Kourouma, F; Sellin, J H

2003-12-01

Diet plays an important role in promoting and/or preventing colon cancer; however, the effects of specific nutrients remain uncertain because of the difficulties in correlating epidemiological and basic observations. Transmissible murine colonic hyperplasia (TMCH) induced by Citrobacter rodentium, causes significant hyperproliferation and hyperplasia in the mouse distal colon and increases the risk of subsequent neoplasia. We have recently shown that TMCH is associated with an increased abundance of cellular beta-catenin and its nuclear translocation coupled with up-regulation of its downstream targets, c-myc and cyclin D1. In this study, we examined the effects of two putatively protective nutrients, calcium and soluble fibre pectin, on molecular events linked to proliferation in the colonic epithelium during TMCH. Dietary intervention incorporating changes in calcium [high (1.0%) and low (0.1%)] and alterations in fibre content (6% pectin and fibre-free) were compared with the standard AIN-93 diet (0.5% calcium, 5% cellulose), followed by histomorphometry and immunochemical assessment of potential oncogenes. Dietary interventions did not alter the time course of Citrobacter infection. Both 1.0% calcium and 6% pectin diet inhibited increases in proliferation and crypt length typically seen in TMCH. Neither the low calcium nor fibre-free diets had significant effect. Pectin diet blocked increases in cellular beta-catenin, cyclin D1 and c-myc levels associated with TMCH by 70%, whereas neither high nor low calcium diet had significant effect on these molecules. Diets supplemented with either calcium or pectin therefore, exert anti-proliferative effects in mouse distal colon involving different molecular pathways. TMCH is thus a diet-sensitive model for examining the effect of specific nutrients on molecular characteristics of the pre-neoplastic colonic epithelium.

Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth

Science.gov (United States)

Kim, EuiJoo

2017-01-01

Introduction The regulation of reactive oxygen species (ROS) exists as a therapeutic target for cancer treatments. Previous studies have shown that ursodeoxycholic acid (UDCA) suppresses the proliferation of colon cancer cells. The aim of this study was to evaluate the effect of UDCA upon the proliferation of colon cancer cells as a direct result of the regulation of ROS. Method Colon cancer cell lines (HT29 and HCT116) were treated with UDCA. The total number of cells and the number of dead cells were determined using cell counters. A fluorescein isothiocyanate-bromodeoxyuridine flow kit was used to analyze cell cycle variations. Upon exposure to UDCA, the protein levels of p27, p21, CDK2, CDK4 and CDK6 were determined using western blotting, and qRT-PCR was used to determine levels of mRNA. We preformed dichlorofluorescindiacetate (DCF-DA) staining to detect alteration of intracellular ROS using fluorescence activated cell sorting (FACS). Colon cancer stem-like cell lines were generated by tumorsphere culture and treated with UDCA for seven days. The total number of tumorspheres was determined using microscopy. Results We found that UDCA reduced the total number of colon cancer cells, but did not increase the number of dead cells. UDCA inhibited the G1/S and G2/M transition phases in colon cancer cells. UDCA induced expression of cell cycle inhibitors such as p27 and p21. However, it was determined that UDCA suppressed levels of CDK2, CDK4, and CDK6. UDCA regulated intracellular ROS generation in colon cancer cells, and induced activation of Erk1/2. Finally, UDCA inhibited formation of colon cancer stem-like cells. Conclusion Our results indicate that UDCA suppresses proliferation through regulation of oxidative stress in colon cancer cells, as well as colon cancer stem-like cells. PMID:28708871

Plasma levels of α-tocopherol, -tocopherol and selenium in patients ...

African Journals Online (AJOL)

user

2014-08-09

Aug 9, 2014 ... No correlation between. -tocopherol and selenium in PCa subjects, but weak and positive correlation exists in .... consistently among smokers where free radicals .... European perspective on vitamin E: Current knowledge and ...

The α-tocopherol transfer protein is essential for vertebrate embryogenesis.

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Galen W Miller

Full Text Available The hepatic α-tocopherol transfer protein (TTP is required for optimal α-tocopherol bioavailability in humans; mutations in the human TTPA gene result in the heritable disorder ataxia with vitamin E deficiency (AVED, OMIM #277460. TTP is also expressed in mammalian uterine and placental cells and in the human embryonic yolk-sac, underscoring TTP's significance during fetal development. TTP and vitamin E are essential for productive pregnancy in rodents, but their precise physiological role in embryogenesis is unknown. We hypothesize that TTP is required to regulate delivery of α-tocopherol to critical target sites in the developing embryo. We tested to find if TTP is essential for proper vertebrate development, utilizing the zebrafish as a non-placental model. We verify that TTP is expressed in the adult zebrafish and its amino acid sequence is homologous to the human ortholog. We show that embryonic transcription of TTP mRNA increases >7-fold during the first 24 hours following fertilization. In situ hybridization demonstrates that Ttpa transcripts are localized in the developing brain, eyes and tail bud at 1-day post fertilization. Inhibiting TTP expression using oligonucleotide morpholinos results in severe malformations of the head and eyes in nearly all morpholino-injected embryos (88% compared with 5.6% in those injected with control morpholinos or 1.7% in non-injected embryos. We conclude that TTP is essential for early development of the vertebrate central nervous system.

Preparation of fluorescent tocopherols for use in protein binding and localization with the alpha-tocopherol transfer protein.

Science.gov (United States)

Nava, Phillip; Cecchini, Matt; Chirico, Sara; Gordon, Heather; Morley, Samantha; Manor, Danny; Atkinson, Jeffrey

2006-06-01

Sixteen fluorescent analogues of the lipid-soluble antioxidant vitamin alpha-tocopherol were prepared incorporating fluorophores at the terminus of omega-functionalized 2-n-alkyl-substituted chromanols (1a-d and 4a-d) that match the methylation pattern of alpha-tocopherol, the most biologically active form of vitamin E. The fluorophores used include 9-anthroyloxy (AO), 7-nitrobenz-2-oxa-1,3-diazole (NBD), N-methyl anthranilamide (NMA), and dansyl (DAN). The compounds were designed to function as fluorescent reporter ligands for protein-binding and lipid transfer assays. The fluorophores were chosen to maximize the fluorescence changes observed upon moving from an aqueous environment (low fluorescence intensity) to an hydrophobic environment such as a protein's binding site (high fluorescence intensity). Compounds 9d (anthroyloxy) and 10d (nitrobenzoxadiazole), having a C9-carbon chain between the chromanol and the fluorophore, were shown to bind specifically and reversibly to recombinant human tocopherol transfer protein (alpha-TTP) with dissociation constants of approximately 280 and 60 nM, respectively, as compared to 25 nM for the natural ligand 2R,4'R,8'R-alpha-tocopherol. Thus, compounds have been prepared that allow the investigation of the rate of alpha-TTP-mediated inter-membrane transfer of alpha-tocopherol and to investigate the mechanism of alpha-TTP function at membranes of different composition.

An in vitro evaluation of antioxidant and colonic microbial profile levels following mushroom consumption.

Science.gov (United States)

Vamanu, Emanuel; Pelinescu, Diana; Avram, Ionela; Nita, Sultana

2013-01-01

The biological activity of mushroom consumption is achieved by the antioxidant effect of constituent biomolecules released during digestion. In the following study, the consumption of mushroom fungi was determined to increase the number of Lactobacillus and Bifidobacterium strains within the colon. The main phenolic antioxidant compounds identified were both gentisic and homogentisic acids. Moreover, the flavonoid catechin as well as a significant amount of δ - and γ-tocopherols was determined. The amount of Lactobacillus and Bifidobacterium strains from different sections of the human colon was significantly correlated with levels of antioxidative biomolecules. The experimental data clearly demonstrate a significant impact of mushroom consumption on the fermentative function of microorganisms in the human colon, resulting in the homeostasis of normal physiological colonic functions.

Genetic Analysis of Reduced γ-Tocopherol Content in Ethiopian Mustard Seeds.

Science.gov (United States)

García-Navarro, Elena; Fernández-Martínez, José M; Pérez-Vich, Begoña; Velasco, Leonardo

2016-01-01

Ethiopian mustard (Brassica carinata A. Braun) line BCT-6, with reduced γ-tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced γ-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both γ- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of γ-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of γ-tocopherol is required.

Genetic Analysis of Reduced γ-Tocopherol Content in Ethiopian Mustard Seeds

Directory of Open Access Journals (Sweden)

Elena García-Navarro

2016-01-01

Full Text Available Ethiopian mustard (Brassica carinata A. Braun line BCT-6, with reduced γ-tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced γ-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both γ- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of γ-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of γ-tocopherol is required.

Tocopherols and tocotrienols plasma levels are associated with cognitive impairment.

Science.gov (United States)

Mangialasche, Francesca; Xu, Weili; Kivipelto, Miia; Costanzi, Emanuela; Ercolani, Sara; Pigliautile, Martina; Cecchetti, Roberta; Baglioni, Mauro; Simmons, Andrew; Soininen, Hilkka; Tsolaki, Magda; Kloszewska, Iwona; Vellas, Bruno; Lovestone, Simon; Mecocci, Patrizia

2012-10-01

Vitamin E includes 8 natural compounds (4 tocopherols, 4 tocotrienols) with potential neuroprotective activity. α-Tocopherol has mainly been investigated in relation to cognitive impairment. We examined the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD. Copyright © 2012 Elsevier Inc. All rights reserved.

Mono-colonization with Lactobacillus acidophilus NCFM affects the intestinal metabolome in mice

DEFF Research Database (Denmark)

Roager, Henrik Munch; Sulek, Karolina; Skov, Kasper

(NCFM) on the intestinal metabolome (jejunum, caecum, and colon) in mice by comparing NCFM mono-colonized (MC) mice with GF mice using liquid chromatography coupled to mass-spectrometry (LC-MS). The study adds to existing evidence that NCFM in vivo affects the bile acid signature of mice......-tocopherol acetate) in higher levels in the intestine of GF mice compared to MC mice, suggesting that NCFM either metabolizes the compound or indirectly affects the absorption by changing the metabolome in the intestine. The use of NCFM to increase the uptake of vitamin E supplements in humans and animals...

Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.

LENUS (Irish Health Repository)

Alzamora, Rodrigo

2011-05-08

Excessive Cl(-) secretion is the driving force for secretory diarrhea. 17β-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17β-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17β-estradiol on cholera toxin and heat-stable enterotoxin induced Cl(-) secretion in rat colonic mucosal sheets was studied by current-voltage clamping. Selective permeabilization of apical or basolateral membranes with amphotericin B or nystatin was used to isolate basolateral K(+) channel and apical Cl(-) channel activity, respectively. 17β-Estradiol dose-dependently inhibited secretory responses to both toxins with IC(50) values of approximately 1nM. This effect was female-gender specific, with no inhibition observed in male tissues. 17β-Estradiol responses were insensitive to the pure anti-estrogen ICI 182,720. 17β-Estradiol exerted its effects downstream of enterotoxin-induced production of second messengers (cAMP and cGMP) but was dependent on PKCδ activation. In nystatin-permeabilized tissues, apical Cl(-) currents were unaffected by 17β-estradiol treatment while basolateral K(+) current was profoundly inhibited by the hormone. This current was sensitive to the specific KCNQ1 channel inhibitors chromanol 293B and HMR-1556. In conclusion, 17β-estradiol inhibits enterotoxin-induced Cl(-) secretion via a PKCδ-dependent mechanism involving inhibition of basolateral KCNQ1 channels. These data elucidate mechanisms of 17β-estradiol inhibition of Cl(-) secretion induced by enterotoxins in intestinal epithelia, which may be relevant for the treatment of diarrheal diseases.

Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon.

LENUS (Irish Health Repository)

Alzamora, Rodrigo

2012-02-01

Excessive Cl(-) secretion is the driving force for secretory diarrhea. 17beta-Estradiol has been shown to inhibit Cl(-) secretion in rat distal colon through a nongenomic pathway. We examined whether 17beta-estradiol inhibits Cl(-) secretion in an animal model of secretory diarrhea and the downstream effectors involved. The effect of 17beta-estradiol on cholera toxin and heat-stable enterotoxin induced Cl(-) secretion in rat colonic mucosal sheets was studied by current-voltage clamping. Selective permeabilization of apical or basolateral membranes with amphotericin B or nystatin was used to isolate basolateral K(+) channel and apical Cl(-) channel activity, respectively. 17beta-Estradiol dose-dependently inhibited secretory responses to both toxins with IC(50) values of approximately 1nM. This effect was female-gender specific, with no inhibition observed in male tissues. 17beta-Estradiol responses were insensitive to the pure anti-estrogen ICI 182,720. 17beta-Estradiol exerted its effects downstream of enterotoxin-induced production of second messengers (cAMP and cGMP) but was dependent on PKCdelta activation. In nystatin-permeabilized tissues, apical Cl(-) currents were unaffected by 17beta-estradiol treatment while basolateral K(+) current was profoundly inhibited by the hormone. This current was sensitive to the specific KCNQ1 channel inhibitors chromanol 293B and HMR-1556. In conclusion, 17beta-estradiol inhibits enterotoxin-induced Cl(-) secretion via a PKCdelta-dependent mechanism involving inhibition of basolateral KCNQ1 channels. These data elucidate mechanisms of 17beta-estradiol inhibition of Cl(-) secretion induced by enterotoxins in intestinal epithelia, which may be relevant for the treatment of diarrheal diseases.

Irradiation Effect on Oxidative Condition and Tocopherol Content of Vegetable Oils

Directory of Open Access Journals (Sweden)

Konstantinos Sflomos

2007-06-01

Full Text Available The effect on induction period and tocopherol content after γ-irradiation onsamples of olive oil and seed oils (sunflower and soybean was determined. In seed oilsamples 0, 100, 200 and 300 ppm of δ-tocopherol were added before irradiation with 1, 2and 3kGy. The results of induction period showed that, after irradiation, all samplespresented a significant decreased in resistance to oxidation. However, this decrease wasminimized when δ-tocopherol was added. Irradiation significantly decreased the level oftocopherols. δ-Tocopherol appeared more sensitive in irradiation process than α- andγ-tocopherol. The addition of δ-tocopherol significantly reduced, in most cases, thedepletion of the other tocopherols.

Effects of oral micellized natural vitamin E (D-α-tocopherol) v. syntheric vitamin E (DL-α-tocopherol) in feed on α-tocopherol levels, stereoisomer distribution, oxidative stress and the immune response in piglets

DEFF Research Database (Denmark)

Amazan, D; Cordero, G; López-Bote, C J

2014-01-01

This study evaluated the strategy of supplementing oral micellized natural vitamin E (d-α-tocopherol) to either piglets and/or sows on α-tocopherol concentrations in piglets serum and tissues after weaning. One first experiment tested the influence of the vitamin E supplementation source (natural...... supplementation on some of these parameters in piglets. Oral supplementation to sows with natural vitamin E as a micellized form (d-α-tocopherol) at the lowest dose produced a similar concentration of α-tocopherol in serum at days 2, 14 and 28 postpartum to those supplemented with threefold higher dose.......001) and lower (Pimportance of sow over piglet vitamin E supplementation was observed on stereoisomer distribution in piglets. Low doses of oral natural vitamin E supplementation...

Inhibition of autophagy exerts anti-colon cancer effects via apoptosis induced by p53 activation and ER stress

International Nuclear Information System (INIS)

Sakitani, Kosuke; Hirata, Yoshihiro; Hikiba, Yohko; Hayakawa, Yoku; Ihara, Sozaburo; Suzuki, Hirobumi; Suzuki, Nobumi; Serizawa, Takako; Kinoshita, Hiroto; Sakamoto, Kei; Nakagawa, Hayato; Tateishi, Keisuke; Maeda, Shin; Ikenoue, Tsuneo; Kawazu, Shoji; Koike, Kazuhiko

2015-01-01

Although some molecularly targeted drugs for colorectal cancer are used clinically and contribute to a better prognosis, the current median survival of advanced colorectal cancer patients is not sufficient. Autophagy, a basic cell survival mechanism mediated by recycling of cellular amino acids, plays an important role in cancer. Recently, autophagy has been highlighted as a promising new molecular target. The unfolded protein response (UPR) reportedly act in complementary fashion with autophagy in intestinal homeostasis. However, the roles of UPR in colon cancer under autophagic inhibition remain to be elucidated. We aim to clarify the inhibitory effect of autophagy on colon cancer. We crossed K19 CreERT and Atg5 flox/flox mice to generate Atg5 flox/flox /K19 CreERT mice. Atg5 flox/flox /K19 CreERT mice were first treated with azoxymethane/dextran sodium sulfate and then injected with tamoxifen to inhibit autophagy in CK19-positive epithelial cells. To examine the anti-cancer mechanisms of autophagic inhibition, we used colon cancer cell lines harboring different p53 gene statuses, as well as small interfering RNAs (siRNAs) targeting Atg5 and immunoglobulin heavy-chain binding protein (BiP), a chaperone to aid folding of unfolded proteins. Colon tumors in Atg5 flox/flox /K19 CreERT mice showed loss of autophagic activity and decreased tumor size (the total tumor diameter was 28.1 mm in the control and 20.7 mm in Atg5 flox/flox /K19 CreERT mice, p = 0.036). We found that p53 and UPR/endoplasmic reticulum (ER) stress-related proteins, such as cleaved caspase 3, and CAAT/enhancer-binding protein homologous protein, are up-regulated in colon tumors of Atg5 flox/flox /K19 CreERT mice. Although Atg5 and BiP silencing, respectively, increased apoptosis in p53 wild type cells, Atg5 silencing alone did not show the same effect on apoptosis in p53 mutant cells. However, co-transfection of Atg5 and BiP siRNAs led to increased apoptosis in p53 mutant cells. Blocking autophagy

Tocopherol in irradiation of temporary hypoxic tumours

International Nuclear Information System (INIS)

Kaagerud, A.; Lund, N.; Peterson, H.I.

1981-01-01

The influence of tocopherol on the effect of local irradiation under induced ischaemia by temporary tourniquet of two rat tumours transplanted intramuscularly into one hindleg was evaluated. An impaired retardation of growth rate occurred in tumours irradiated under ischaemia. This effect was eliminated by pretreatment of animals with tocopherol. In separate experiments the method of inducing ischaemia was investigated by MDO-electrode measurements of tumour tissue oxygen pressure. A significant tumour hypoxia was found under tourniquet of the tumour-bearing leg of the animals. Pretreatment with tocopherol did not influence the tumour pO 2 . (Auth.)

Tocopherol synthesis from homogentisate in Capsicum anuum L. (yellow pepper) chromoplast membranes: evidence for tocopherol cyclase.

OpenAIRE

Arango, Y; Heise, K P

1998-01-01

The present study shows for the first time appreciable tocopherol cyclase activities in plastidial membrane preparations of Capsicum annuum L. (yellow pepper) fruits. When chromoplast membranes from yellow peppers were incubated with [3H]homogentisate and phytyl pyrophosphate under strictly reducing conditions, all biosynthesis precursors were labelled. The main labelling was found in gamma-tocopherol. These observations contradict the hypothesis that assigns a rate-limiting function to tocop...

Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

DEFF Research Database (Denmark)

Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof

1992-01-01

Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins

International Nuclear Information System (INIS)

Traber, M.G.; Burton, G.W.; Ingold, K.U.; Kayden, H.J.

1990-01-01

Five subjects ingested in a single oral dose containing 50 mg each of 2R,4'R,8'R-alpha-(5,7-(C2H3)2)tocopheryl acetate (d6-RRR-alpha-tocopheryl acetate) with natural stereochemistry, and of 2S,4'R,8'R-alpha-(5-C2H3)tocopheryl acetate (d3-SRR-alpha-tocopheryl acetate). These are two of eight stereoisomers in synthetic vitamin E. By day 1 the plasma and red blood cells were enriched fourfold with d6-RRR-alpha-tocopherol (P less than 0.004). The ratio of d6-RRR-/d2-SRR- further increased over the succeeding 4 days, because the d3-SRR- decreased at a faster rate than did the d6-RRR-stereoisomer. Plasma and lipoproteins were isolated at intervals during the first day, and daily for 3 days, from four additional subjects fed a mixture of equal amounts of the deuterated tocopherols. The plasma contained similar concentrations of the two forms until 11 h, when the d6-RRR-alpha-tocopherol concentration became significantly greater (P less than 0.05). The chylomicrons contained similar concentrations of the two deuterated tocopherols, but the VLDL (very low density lipoproteins) became preferentially enriched in d6-RRR-alpha-tocopherol by 11 h. The pattern of the deuterated tocopherols shows that during chylomicron catabolism all of the plasma lipoproteins were labeled equally with both tocopherols, but that during the subsequent VLDL catabolism the low and high density lipoproteins became enriched in d6-RRR-alpha-tocopherol. These results suggest the existence of a mechanism in the liver for assembling VLDL preferentially enriched in RRR- relative to SRR-alpha-tocopherol

Comparative Analysis of Tocopherol Biosynthesis Genes and Its Transcriptional Regulation in Soybean Seeds.

Science.gov (United States)

T, Vinutha; Bansal, Navita; Kumari, Khushboo; Prashat G, Rama; Sreevathsa, Rohini; Krishnan, Veda; Kumari, Sweta; Dahuja, Anil; Lal, S K; Sachdev, Archana; Praveen, Shelly

2017-12-20

Tocopherols composed of four isoforms (α, β, γ, and δ) and its biosynthesis comprises of three pathways: methylerythritol 4-phosphate (MEP), shikimate (SK) and tocopherol-core pathways regulated by 25 enzymes. To understand pathway regulatory mechanism at transcriptional level, gene expression profile of tocopherol-biosynthesis genes in two soybean genotypes was carried out, the results showed significantly differential expression of 5 genes: 1-deoxy-d-xylulose-5-P-reductoisomerase (DXR), geranyl geranyl reductase (GGDR) from MEP, arogenate dehydrogenase (TyrA), tyrosine aminotransferase (TAT) from SK and γ-tocopherol methyl transferase 3 (γ-TMT3) from tocopherol-core pathways. Expression data were further analyzed for total tocopherol (T-toc) and α-tocopherol (α-toc) content by coregulation network and gene clustering approaches, the results showed least and strong association of γ-TMT3/tocopherol cyclase (TC) and DXR/DXS, respectively, with gene clusters of tocopherol biosynthesis suggested the specific role of γ-TMT3/TC in determining tocopherol accumulation and intricacy of DXR/DXS genes in coordinating precursor pathways toward tocopherol biosynthesis in soybean seeds. Thus, the present study provides insight into the major role of these genes regulating the tocopherol synthesis in soybean seeds.

Nanoparticles with entrapped {alpha}-tocopherol: synthesis, characterization, and controlled release

Energy Technology Data Exchange (ETDEWEB)

Zigoneanu, Imola Gabriela [101 E B Doran Building, BAE Department, Louisiana State University Agricultural Center, Baton Rouge, LA 70803 (United States); Astete, Carlos Ernesto [110 E B Doran Building, BAE Department, Louisiana State University Agricultural Center, Baton Rouge, LA 70803 (United States); Sabliov, Cristina Mirela [141 E B Doran Building, BAE Department, Louisiana State University Agricultural Center, Baton Rouge, LA 70803 (United States)], E-mail: csabliov@lsu.edu

2008-03-12

An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped {alpha}-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of {alpha}-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of {alpha}-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% {alpha}-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the {alpha}-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% {alpha}-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% {alpha}-tocopherol theoretical loading (34% released in the first hour)

Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release

International Nuclear Information System (INIS)

Zigoneanu, Imola Gabriela; Astete, Carlos Ernesto; Sabliov, Cristina Mirela

2008-01-01

An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped α-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of α-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of α-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% α-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the α-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% α-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% α-tocopherol theoretical loading (34% released in the first hour)

Saccharomyces boulardii Protease Inhibits the Effects of Clostridium difficile Toxins A and B in Human Colonic Mucosa

Science.gov (United States)

Castagliuolo, Ignazio; Riegler, Martin F.; Valenick, Leyla; LaMont, J. Thomas; Pothoulakis, Charalabos

1999-01-01

Saccharomyces boulardii is a nonpathogenic yeast used in the treatment of Clostridium difficile diarrhea and colitis. We have reported that S. boulardii inhibits C. difficile toxin A enteritis in rats by releasing a 54-kDa protease which digests the toxin A molecule and its brush border membrane (BBM) receptor (I. Castagliuolo, J. T. LaMont, S. T. Nikulasson, and C. Pothoulakis, Infect. Immun. 64:5225–5232, 1996). The aim of this study was to further evaluate the role of S. boulardii protease in preventing C. difficile toxin A enteritis in rat ileum and determine whether it protects human colonic mucosa from C. difficile toxins. A polyclonal rabbit antiserum raised against purified S. boulardii serine protease inhibited by 73% the proteolytic activity present in S. boulardii conditioned medium in vitro. The anti-protease immunoglobulin G (IgG) prevented the action of S. boulardii on toxin A-induced intestinal secretion and mucosal permeability to [3H]mannitol in rat ileal loops, while control rabbit IgG had no effect. The anti-protease IgG also prevented the effects of S. boulardii protease on digestion of toxins A and B and on binding of [3H]toxin A and [3H]toxin B to purified human colonic BBM. Purified S. boulardii protease reversed toxin A- and toxin B-induced inhibition of protein synthesis in human colonic (HT-29) cells. Furthermore, toxin A- and B-induced drops in transepithelial resistance in human colonic mucosa mounted in Ussing chambers were reversed by 60 and 68%, respectively, by preexposing the toxins to S. boulardii protease. We conclude that the protective effects of S. boulardii on C. difficile-induced inflammatory diarrhea in humans are due, at least in part, to proteolytic digestion of toxin A and B molecules by a secreted protease. PMID:9864230

Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse

Science.gov (United States)

Schill, Ellen Merrick; Lake, Jonathan I.; Tusheva, Olga A.; Nagy, Nandor; Bery, Saya K.; Foster, Lynne; Avetisyan, Marina; Johnson, Stephen L.; Stenson, William F.; Goldstein, Allan M.; Heuckeroth, Robert O.

2016-01-01

Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/− mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children. PMID:26586201

Influence of major structural features of tocopherols and tocotrienols on their omega-oxidation by tocopherol-omega-hydroxylase.

Science.gov (United States)

Sontag, Timothy J; Parker, Robert S

2007-05-01

Human cytochrome P450 4F2 (CYP4F2) catalyzes the initial omega-hydroxylation reaction in the metabolism of tocopherols and tocotrienols to carboxychromanols and is, to date, the only enzyme shown to metabolize vitamin E. The objective of this study was to characterize this activity, particularly the influence of key features of tocochromanol substrate structure. The influence of the number and positions of methyl groups on the chromanol ring, and of stereochemistry and saturation of the side chain, were explored using HepG2 cultures and microsomal reaction systems. Human liver microsomes and microsomes selectively expressing recombinant human CYP4F2 exhibited substrate activity patterns similar to those of HepG2 cells. Although activity was strongly associated with substrate accumulation by cells or microsomes, substantial differences in specific activities between substrates remained under conditions of similar microsomal membrane substrate concentration. Methylation at C5 of the chromanol ring was associated with markedly low activity. Tocotrienols exhibited much higher Vmax values than their tocopherol counterparts. Side chain stereochemistry had no effect on omega-hydroxylation of alpha-tocopherol (alpha-TOH) by any system. Kinetic analysis of microsomal CYP4F2 activity revealed Michaelis-Menten kinetics for alpha-TOH but allosteric cooperativity for other vitamers, especially tocotrienols. Additionally, alpha-TOH was a positive effector of omega-hydroxylation of other vitamers. These results indicate that CYP4F2-mediated tocopherol-omega-hydroxylation is a central feature underlying the different biological half-lives, and therefore biopotencies, of the tocopherols and tocotrienols.

Novel urinary metabolite of d-delta-tocopherol in rats

International Nuclear Information System (INIS)

Chiku, S.; Hamamura, K.; Nakamura, T.

1984-01-01

A novel metabolite of d-delta-tocopherol was isolated from the urine of rats given d-3,4-[ 3 H 2 ]-delta-tocopherol intravenously. The metabolite was collected from the urine of rats given d-delta-tocopherol in the same manner as that of the labeled compound. It was found that the metabolites consisted of sulfate conjugates. The portion of the major metabolite released with sulfatase was determined to be 2,8-dimethyl-2-(2'-carboxyethyl)-6-chromanol by infrared spectra, nuclear magnetic resonance spectra, and mass spectra. The proposed structure was confirmed by comparing the analytical results with those of a synthetically derived compound. As a result of the structural elucidation of this novel metabolite, a pathway for the biological transformation of delta-tocopherol is proposed which is different from that of alpha-tocopherol. A characteristic feature of the pathway is the absence of any opening of the chroman ring throughout the sequence

Ultra-performance liquid chromatographic determination of tocopherols and retinol in human plasma.

Science.gov (United States)

Bell, Edward C; John, Mathew; Hughes, Rodney J; Pham, Thu

2014-10-01

A rapid, selective and sensitive ultra-performance liquid chromatography method has been developed for the detection and quantification of tocopherols and retinol in human plasma. Alpha-tocopherol, gamma-tocopherol and retinol are assayed using fluorescence detection. Excitation/emission wavelengths are 295/330 nm and 325/470 nm for the analysis of both tocopherols and retinol, respectively. Retinol acetate is employed as the internal standard. The reversed-phase method incorporates gradient elution with a mobile phase consisting of methanol and acetonitrile. Separation of vitamin compounds is achieved using a bridged ethyl hybrid C18 column. The retention times for retinol, retinol acetate, gamma-tocopherol and alpha-tocopherol are 1.6, 1.8, 3.9 and 4.3 min, respectively. The limits of quantification for retinol, gamma-tocopherol and alpha-tocopherol were 0.02, 0.02 and 0.1 µg/mL, respectively. The assay method is suitable for the analysis of tocopherols and retinol in human plasma. The method may be applied following the ingestion of foods fortified with these fat-soluble vitamins. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Temperature dependence of autoxidation of perilla oil and tocopherol degradation.

Science.gov (United States)

Wang, Seonyeong; Hwang, Hyunsuk; Yoon, Sukhoo; Choe, Eunok

2010-08-01

Temperature dependence of the autoxidation of perilla oil and tocopherol degradation was studied with corn oil as a reference. The oils were oxidized in the dark at 20, 40, 60, and 80 degrees C. Oil oxidation was determined by peroxide and conjugated dienoic acid values. Tocopherols in the oils were quantified by HPLC. The oxidation of both oils increased with oxidation time and temperature. Induction periods for oil autoxidation decreased with temperature, and were longer in corn oil than in perilla oil, indicating higher sensitivity of perilla oil to oxidation. However, time lag for tocopherol degradation was longer in perilla oil, indicating higher stability of tocopherols in perilla oil than in corn oil. Activation energies for oil autoxidation and tocopherol degradation were higher in perilla oil (23.9 to 24.2, 9.8 kcal/mol, respectively) than in corn oil (12.5 to 15.8, 8.8 kcal/mol, respectively) indicating higher temperature-dependence in perilla oil. Higher stability of tocopherols in perilla oil was highly related with polyphenols. The study suggests that more careful temperature control is required to decrease the autoxidation of perilla oil than that of corn oil, and polyphenols contributed to the oxidative stability of perilla oil by protecting tocopherols from degradation, especially at the early stage of oil autoxidation.

Rapid Estimation of Tocopherol Content in Linseed and Sunflower Oils-Reactivity and Assay

Directory of Open Access Journals (Sweden)

Tjaša Prevc

2015-08-01

Full Text Available The reactivity of tocopherols with 2,2-diphenyl-1-picrylhydrazyl (DPPH was studied in model systems in order to establish a method for quantifying vitamin E in plant oils. The method was optimized with respect to solvent composition of the assay medium, which has a large influence on the course of reaction of tocopherols with DPPH. The rate of reaction of α-tocopherol with DPPH is higher than that of γ-tocopherol in both protic and aprotic solvents. In ethyl acetate, routinely applied for the analysis of antioxidant potential (AOP of plant oils, reactions of tocopherols with DPPH are slower and concentration of tocopherols in the assay has a large influence on their molar reactivity. In 2-propanol, however, two electrons are exchanged for both α- and γ-tocopherols, independent of their concentration. 2-propanol is not toxic and is fully compatible with polypropylene labware. The chromatographically determined content of tocopherols and their molar reactivity in the DPPH assay reveal that only tocopherols contribute to the AOP of sunflower oil, whereas the contribution of tocopherols to the AOP of linseed oil is 75%. The DPPH assay in 2-propanol can be applied for rapid and cheap estimation of vitamin E content in plant oils where tocopherols are major antioxidants.

Rapid Estimation of Tocopherol Content in Linseed and Sunflower Oils-Reactivity and Assay.

Science.gov (United States)

Prevc, Tjaša; Levart, Alenka; Cigić, Irena Kralj; Salobir, Janez; Ulrih, Nataša Poklar; Cigić, Blaž

2015-08-13

The reactivity of tocopherols with 2,2-diphenyl-1-picrylhydrazyl (DPPH) was studied in model systems in order to establish a method for quantifying vitamin E in plant oils. The method was optimized with respect to solvent composition of the assay medium, which has a large influence on the course of reaction of tocopherols with DPPH. The rate of reaction of α-tocopherol with DPPH is higher than that of γ-tocopherol in both protic and aprotic solvents. In ethyl acetate, routinely applied for the analysis of antioxidant potential (AOP) of plant oils, reactions of tocopherols with DPPH are slower and concentration of tocopherols in the assay has a large influence on their molar reactivity. In 2-propanol, however, two electrons are exchanged for both α- and γ-tocopherols, independent of their concentration. 2-propanol is not toxic and is fully compatible with polypropylene labware. The chromatographically determined content of tocopherols and their molar reactivity in the DPPH assay reveal that only tocopherols contribute to the AOP of sunflower oil, whereas the contribution of tocopherols to the AOP of linseed oil is 75%. The DPPH assay in 2-propanol can be applied for rapid and cheap estimation of vitamin E content in plant oils where tocopherols are major antioxidants.

α-TOCOPHEROL β-OXIDATION LOCALIZED TO RAT LIVER MITOCHONDRIA

OpenAIRE

Mustacich, Debbie J.; Leonard, Scott W.; Patel, Neha K.; Traber, Maret G.

2009-01-01

Approximately 40% of Americans take dietary supplements, including vitamin E (α-tocopherol). Unlike other fat-soluble vitamins, α-tocopherol is not accumulated to toxic levels. Rather tissue levels are tightly regulated, in part via increased hepatic metabolism and excretion that could, theoretically, alter metabolism of drugs, environmental toxins and other nutrients. To date, in vivo subcellular location(s) of α-tocopherol metabolism have not been identified. The proposed pathway of α-tocop...

Simulation and thermodynamic modeling of the extraction of tocopherol from a synthetic mixture of tocopherol, squalene and CO2

Directory of Open Access Journals (Sweden)

M.F. Mendes

2000-12-01

Full Text Available Soybean oil is the most consumed vegetable oil in the world, representing 54% of the total world production. Brazil is the second country in the world that produces and export soybean seeds, almost 20%. One of the most important by-product of the soybean oil is the deodorizer distillate, commonly known as soybean sludge. This residue is rich in many high value compounds as tocopherols, squalene and sterols. Tocopherols are the major components in the deodorized distillated due to their characteristics as an antioxidant agent. So, the objective of this work is to study the concentration of tocopherols presented in this raw material, using the operational conditions obtained from the equilibrium data and using supercritical carbon dioxide as a solvent. The deodorizer distillate is a complex mixture of more than 200 components, so a synthetic mixture was chosen to represent the deodorizer distillate. The synthetic mixture used in this work is composed by tocopherols, fatty acids and squalene. The simulation was carried out using ASPEN+ simulator and the LCVM thermodynamic model was used to correlate the available equilibrium data.

Calcimimetic R568 inhibits tetrodotoxin-sensitive colonic electrolyte secretion and reduces c-fos expression in myenteric neurons.

Science.gov (United States)

Sun, Xiangrong; Tang, Lieqi; Winesett, Steven; Chang, Wenhan; Cheng, Sam Xianjun

2018-02-01

Calcium-sensing receptor (CaSR) is expressed on neurons of both submucosal and myenteric plexuses of the enteric nervous system (ENS) and the CaSR agonist R568 inhibited Cl - secretion in intestine. The purpose of this study was to localize the primary site of action of R568 in the ENS and to explore how CaSR regulates secretion through the ENS. Two preparations of rat proximal and distal colon were used. The full-thickness preparation contained both the submucosal and myenteric plexuses, whereas for the "stripped" preparation the myenteric plexus with the muscle layers was removed. Both preparations were mounted onto Ussing chambers and Cl - secretory responses were compared by measuring changes in short circuit current (I sc ). Two tissue-specific CaSR knockouts (i.e., neuron-specific vs. enterocyte-specific) were generated to compare the effect of R568 on expression of c-fos protein in myenteric neurons by immunocytochemistry. In full-thickness colons, tetrodotoxin (TTX) inhibited I sc , both in proximal and distal colons. A nearly identical inhibition was produced by R568. However, in stripped preparations, while the effect of TTX on I sc largely remained, the effect of R568 was nearly completely eliminated. In keeping with this, R568 reduced c-fos protein expression only in myenteric neurons of wild type mice and mutant mice that contained CaSR in neurons (i.e., villin Cre/Casr flox/flox mice), but not in myenteric neurons of nestin Cre/Casr flox/flox mice in which neuronal cell CaSR was eliminated. These results indicate that R568 exerts its anti-secretory effects predominantly via CaSR-mediated inhibition of neuronal activity in the myenteric plexus. Published by Elsevier Inc.

Engineering Tocopherol Selectivity in α-TTP: A Combined In Vitro/In Silico Study

Science.gov (United States)

Helbling, Rachel E.; Aeschimann, Walter; Simona, Fabio; Stocker, Achim; Cascella, Michele

2012-01-01

We present a combined in vitro/in silico study to determine the molecular origin of the selectivity of -tocopherol transfer protein (-TTP) towards -tocopherol. Molecular dynamics simulations combined to free energy perturbation calculations predict a binding free energy for -tocopherol to -TTP 8.262.13 kcal mol lower than that of -tocopherol. Our calculations show that -tocopherol binds to -TTP in a significantly distorted geometry as compared to that of the natural ligand. Variations in the hydration of the binding pocket and in the protein structure are found as well. We propose a mutation, A156L, which significantly modifies the selectivity properties of -TTP towards the two tocopherols. In particular, our simulations predict that A156L binds preferentially to -tocopherol, with striking structural similarities to the wild-type--tocopherol complex. The affinity properties are confirmed by differential scanning fluorimetry as well as in vitro competitive binding assays. Our data indicate that residue A156 is at a critical position for determination of the selectivity of -TTP. The engineering of TTP mutants with modulating binding properties can have potential impact at industrial level for easier purification of single tocopherols from vitamin E mixtures coming from natural oils or synthetic processes. Moreover, the identification of a -tocopherol selective TTP offers the possibility to challenge the hypotheses for the evolutionary development of a mechanism for -tocopherol selection in omnivorous animals. PMID:23152872

Tocopherol-deficient rice plants display increased sensitivity to photooxidative stress.

Science.gov (United States)

Chen, Defu; Chen, Haiwei; Zhang, Luhua; Shi, Xiaoli; Chen, Xiwen

2014-06-01

Tocopherols are lipophilic antioxidants that are synthesized exclusively in photosynthetic organisms. Despite extensive in vivo characterization of tocopherol functions in plants, their functions in the monocot model plant, rice, remain to be determined. In this study, transgenic rice plants constitutively silenced for homogentisate phytyltransferase (HPT) and tocopherol cyclase (TC) activity were generated. Silencing of HPT and TC resulted in up to a 98 % reduction in foliar tocopherol content relative to the control plants, which was also confirmed by transcript level analysis. When grown under normal conditions, HPT and TC transgenics showed no distinctive phenotype relative to the control plants, except a slight reduction in plant height and a slight decrease in the first leaf length. However, when exposed to high light at low temperatures, HPT and TC transgenics had a significantly higher leaf yellowing index than the control plants. The tocopherol-deficient plants decreased their total individual chlorophyll levels, their chlorophyll a/b ratio, and the maximum photochemical efficiency of photosystem II, whereas increased lipid peroxidation levels relative to the control plants. Tocopherol deficiency had no effect on ascorbate biosynthesis, but induced glutathione, antheraxanthin, and particularly zeaxanthin biosynthesis for compensation under stressful conditions. However, despite these compensation mechanisms, HPT and TC transgenics still exhibited altered phenotypes under high light at low temperatures. Therefore, it is suggested that tocopherols cannot be replaced and play an indispensable role in photoprotection in rice.

First-trimester plasma tocopherols are associated with risk of miscarriage in rural Bangladesh.

Science.gov (United States)

Shamim, Abu Ahmed; Schulze, Kerry; Merrill, Rebecca D; Kabir, Alamgir; Christian, Parul; Shaikh, Saijuddin; Wu, Lee; Ali, Hasmot; Labrique, Alain B; Mehra, Sucheta; Klemm, Rolf D W; Rashid, Mahbubur; Sungpuag, Pongtorn; Udomkesmalee, Emorn; West, Keith P

2015-02-01

Tocopherols were discovered for their role in animal reproduction, but little is known about the contribution of deficiencies of vitamin E to human pregnancy loss. We sought to determine whether higher first-trimester concentrations of α-tocopherol and γ-tocopherol were associated with reduced odds of miscarriage (pregnancy losses tocopherol (tocopherol (tocopherol distribution in women who did not miscarry). In all women, plasma α- and γ-tocopherol concentrations were low [median (IQR): 10.04 μmol/L (8.07-12.35 μmol/L) and 0.66 μmol/L (0.50-0.95 μmol/L), respectively]. In a logistic regression analysis that was adjusted for cholesterol and the other tocopherol, low α-tocopherol was associated with an OR of 1.83 (95% CI: 1.04, 3.20), whereas a low γ-tocopherol concentration was associated with an OR of 0.62 (95% CI: 0.41, 0.93) for miscarriage. Subgroup analyses revealed that opposing ORs were evident only in women with BMI (in kg/m(2)) ≥18.5 and serum ferritin concentration ≤150 μg/L, although low BMI and elevated ferritin conferred stronger risk of miscarriage. In pregnant women in rural Bangladesh, low plasma α-tocopherol was associated with increased risk of miscarriage, and low γ-tocopherol was associated with decreased risk of miscarriage. Maternal vitamin E status in the first trimester may influence risk of early pregnancy loss. The JiVitA-1 study, from which data for this report were derived, was registered at clinicaltrials.gov as NCT00198822. © 2015 American Society for Nutrition.

Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities.

Science.gov (United States)

Direito, Rosa; Lima, Ana; Rocha, João; Ferreira, Ricardo Boavida; Mota, Joana; Rebelo, Patrícia; Fernandes, Adelaide; Pinto, Rui; Alves, Paula; Bronze, Rosário; Sepodes, Bruno; Figueira, Maria-Eduardo

2017-08-01

Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD. Copyright © 2017 Elsevier Inc. All rights reserved.

A Comparison of Natural (D-α-tocopherol and Synthetic (DL-α-tocopherol Acetate Vitamin E Supplementation on the Growth Performance, Meat Quality and Oxidative Status of Broilers

Directory of Open Access Journals (Sweden)

K. Cheng

2016-05-01

Full Text Available The present study was conducted to compare the supplementation of natural (D-α-tocopherol and synthetic (DL-α-tocopherol acetate vitamin E on the growth performance, meat quality, muscular antioxidant capacity and genes expression related to oxidative status of broilers. A total of 144 1 day-old Arbor Acres broiler chicks were randomly allocated into 3 groups with 6 replicates of 8 birds each. Birds were given a basal diet (control group, and basal diet supplemented with either 20 IU D-α-tocopherol or DL-α-tocopherol acetate for 42 days, respectively. The results indicated that treatments did not alter growth performance of broilers (p>0.05. Compared with the control group, concentration of α-tocopherol in the breast muscle was increased by the supplementation of vitamin E (p0.05. It was concluded that vitamin E supplementation, especially the natural vitamin E, can enhance the retention of muscular α-tocopherol, improve meat quality and muscular antioxidant capacity of broilers.

Biodegradable films containing α-tocopherol/β-cyclodextrin complex

International Nuclear Information System (INIS)

Motta, Caroline; Martelli, Silvia M.; Soldi, Valdir; Barreto, Pedro L.M.

2011-01-01

The growing environmental concern about pollution and the need to reduce dependence of plastic industry in relation to non-renewable resources has increased the interest of both researchers and industry in the use of biopolymers. In this work β-cyclodextrin/α-tocopherol complexes were prepared and characterized. In order to obtain polymeric active biofilms, the β-cyclodextrin/α-tocopherol complex was incorporated into a polymeric matrix of carboxymethylcellulose. The β-cyclodextrin/α-tocopherol complex was characterized through of X-ray diffraction and thermogravimetric analysis. The physicochemical properties of the films incorporated with the complex were evaluated through mechanical and colorimetric analysis and moisture sorption isotherm. (author)

Tocopherol Supplementation Reduces NO Production and Pulmonary Inflammatory Response to Bleomycin

Science.gov (United States)

Shi, Jin Dong; Golden, Thea; Guo, Chang-Jiang; Tu, Shui Ping; Scott, Pamela; Lee, Mao-Jung; Yang, Chung S.; Gow, Andrew J.

2013-01-01

Bleomycin causes acute lung injury through production of reactive species and initiation of inflammation. Previous work has shown alteration to the production of reactive oxygen species results in attenuation of injury. Vitamin E, in particular, γ-tocopherol, isoform, has the potential to scavenge reactive oxygen and nitrogen species. This study examines the utility of dietary supplementation with tocopherols in reducing bleomycin-mediated acute lung injury. Male C57BL6/J mice were intratracheally instilled with PBS or 2 units/kg bleomycin. Animals were analyzed 3 and 8 days post instillation at the cellular, tissue, and organ levels. Results showed successful delivery of tocopherols to the lung via dietary supplementation. Also, increases in reactive oxygen and nitrogen species due to bleomycin are normalized in those mice fed tocopherol diet. Injury was not prevented but inflammation progression was altered, in particular macrophage activation and function. Inflammatory scores based on histology demonstrate limited progression of inflammation in those mice treated with bleomycin and fed tocopherol diet compared to control diet. Upregulation of enzymes and cytokines involved in pro-inflammation were limited by tocopherol supplementation. Day 3 functional changes in elastance in response to bleomycin are prevented, however, 8 days post injury the effect of the tocopherol diet is lost. The effect of tocopherol supplementation upon the inflammatory process is demonstrated by a shift in the phenotype of macrophage activation. The effect of these changes on resolution and the progression of pulmonary fibrosis has yet to be elucidated. PMID:23669183

N-end rule pathway inhibition assists colon tumor regression via necroptosis

Directory of Open Access Journals (Sweden)

Pritha Agarwalla

2016-01-01

Full Text Available Recent study has shown that N-end rule pathway, an ubiquitin dependent proteolytic system, counteracts cell death by degrading many antisurvival protein fragments like BCLxL, BRCA1, RIPK1, etc. Inhibition of the N-end rule pathway can lead to metabolic stabilization of proapoptotic protein fragments like RIPK1, thereby sensitizing cells to programmed cell death. Receptor interacting serine-threonine protein kinase-1 (RIPK1 is one of the upstream regulators of programmed necrosis known as necroptosis. Necroptosis is particularly gaining attention of cancer biologists as it provides an alternate therapeutic modality to kill cancer cells, which often evolve multiple strategies to circumvent growth inhibition by apoptosis. Utilizing the over expression of biotin receptor in cancer cells, herein, we report that coadministration of synthetic hetero-bivalent N-end rule inhibitor RFC11 and anticancer drug shikonin solubilized in a stable biotin receptor-targeted liposome exhibited significant synergistic antitumor effect in both subcutaneous and orthotopic mouse colon tumor model through induction of necroptosis with distinctive upregulation of RIPK1. Besides developing a newly targeted formulation for necroptosis induction, this report is the first in vivo evidence demonstrating that potent inhibition of N-end rule pathway can enhance therapeutic efficacy of conventional chemotherapeutics.

Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

LENUS (Irish Health Repository)

Ward, Joseph B J

2012-02-01

Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 +\\/- 2.6 and 38.8 +\\/- 6.7% (n=16; P<\\/=0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

LENUS (Irish Health Repository)

Ward, Joseph B J

2011-02-01

Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 ± 2.6 and 38.8 ± 6.7% (n=16; P≤0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

Cytoprotective effect of tocopherols in hepatocytes cultured with polyunsaturated fatty acids

DEFF Research Database (Denmark)

Mikkelsen, L.; Hansen, Harald S.; Grunnet, N.

1994-01-01

When highly unsaturated fatty acids are added to cell cultures, it can become important to include antioxidants in the culture medium to prevent cytotoxic peroxidation. To find an optimal antioxidant for this purpose, the effect of 50 µM a-tocopherol, ¿-tocopherol, a-tocopheryl acetate, a...... of thiobarbituric acid reactive substances in the cultures was also measured. a-Tocopheryl acid succinate was found to be the most effective cytoprotective compound, followed by N,N'-diphenyl-1,4-phenylenediamine, a- tocopherol, ¿-tocopherol and a-tocopheryl acetate, and a-tocopheryl phosphate was without effect....

Role of neutral ceramidase in colon cancer.

Science.gov (United States)

García-Barros, Mónica; Coant, Nicolas; Kawamori, Toshihiko; Wada, Masayuki; Snider, Ashley J; Truman, Jean-Philip; Wu, Bill X; Furuya, Hideki; Clarke, Christopher J; Bialkowska, Agnieszka B; Ghaleb, Amr; Yang, Vincent W; Obeid, Lina M; Hannun, Yusuf A

2016-12-01

Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells. Inhibition of nCDase resulted in loss of β-catenin and inhibition of ERK, components of pathways relevant for colon cancer development. Furthermore, inhibition of nCDase in a xenograft model delayed tumor growth and increased ceramide while decreasing proliferation. It is noteworthy that mice lacking nCDase treated with azoxymethane were protected from tumor formation. Taken together, these studies show that nCDase is pivotal for regulating initiation and development of colon cancer, and these data suggest that this enzyme is a suitable and novel target for colon cancer therapy.-García-Barros, M., Coant, N., Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H., Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun, Y. A. Role of neutral ceramidase in colon cancer. © FASEB.

miRNA-218-loaded carboxymethyl chitosan - Tocopherol nanoparticle to suppress the proliferation of gastrointestinal stromal tumor growth

Energy Technology Data Exchange (ETDEWEB)

Tu, Lin; Wang, Ming; Zhao, Wen-Yi; Zhang, Zi-Zhen; Tang, De-Feng; Zhang, Ye-Qian [Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Cao, Hui, E-mail: caohui10281@163.com [Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127 (China); Zhang, Zhi-Gang, E-mail: zhangzhiganggz@hotmail.com [State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240 (China)

2017-03-01

Gastrointestinal stromal tumors (GIST) are one of the most common forms of mesenchymal cancers of the gastrointestinal tract. Although chemotherapeutic drugs inhibited the proliferation of GIST, however, sizable proportion of people developed resistance and therefore difficult to treat. In the present study, O-carboxymethyl chitosan (OCMC)-tocopherol polymer conjugate was synthesized and formulated into stable polymeric nanoparticles. The main aim of present study was to increase the therapeutic efficacy of miR-218 in GIST. The mean size of nanoparticles was ~ 110 nm with a spherical shape. The miR-218 NP has been shown inhibit the cell proliferation and exhibited a superior cell apoptosis. The miR-218 NP inhibited the cell invasion and promoted the apoptosis of GIST cancer cells. In the present study, we have successfully showed that KIT1 is the target gene of miR-218 as shown by the luciferase reporter assay. These findings collectively suggest the miR-218 loaded nanoparticle by virtue of effective transfection could act as a tumor suppressor miRNA in the treatment of GIST. - Highlights: • O-carboxymethyl chitosan (OCMC)-tocopherol polymer conjugate was synthesized and formulated in nanoparticles. • The miR-218 NP has been shown inhibit the cell proliferation and exhibited a superior cell apoptosis. • We have successfully showed that KIT1 is the target gene of miR-218 as shown by the luciferase reporter assay.

Prediagnostic serum tocopherol levels and the risk of non-hodgkin lymphoma: the multiethnic cohort.

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Morimoto, Yukiko; Ollberding, Nicholas J; Cooney, Robert V; Wilkens, Lynne R; Franke, Adrian A; Le Marchand, Loïc; Goodman, Marc T; Hernandez, Brenda Y; Kolonel, Laurence N; Maskarinec, Gertraud

2013-11-01

Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high-pressure liquid chromatography/photodiode array detection with NHL risk. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). We observed U-shaped associations with NHL for total and α-tocopherols [Ptrend tocopherols, which consisted primarily of α-tocopherol, were 0.41 (0.25-0.68), 0.52 (0.32-0.85), 0.39 (0.23-0.65), and 0.78 (0.47-1.29) for the second to fifth quintiles as compared with the first. The risk estimates were similar for α-tocopherol but nonsignificant for β- and γ-tocopherol combined and for γ-tocopherol. Adjustment for serum lipids strengthened the nonlinear associations for total and α-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than nonusers (21.32 ± 9.04 vs. 17.72 ± 7.43 μg/mL; P tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL. ©2013 AACR.

Fatty acid, tocopherol and squalene contents of Rosaceae seed oils.

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Matthaus, Bertrand; Özcan, Mehmet Musa

2014-12-01

The aim of current study is to establish the composition of these seeds belong to Rosaceae family with respect to fatty acid, tocopherol and squalene content. The oil contents of seeds varied between 3.49 (Cotoneaster bullatus) to 46.15 g/100 g (Prunus tenella). The main fatty acids of seed oils were oleic (6.50 - 67.11 %), linoleic (22.08 - 68.62 %) and 20:1n-7 (0.10 - 61.59 %). As observed, the oils of seed were rich in linoleic and oleic acids. Total tocopherol contents ranged between 7.06 mg/100 g (Prunus tenella) to 165.74 mg/100 g (Potentilla glandulosa ssp. pseudorupestris). The major tocopherols were γ-tocopherol, ranging from 2.08 mg/100 g to 106.01 mg/100 g; α-tocopherol ranging from 2.86 mg100 g to 74.26 mg/100 g and δ-tocopherol ranging used in this experiment were found between 0.02 mg/100 g (Alchemilla caucasica) to o.29 mg/100 g (Cotoneaster simonsii). These results show that Rosaceae seed oils can be a potential saurce of valuable oil which might be useful for the evaluation of dietary information in important food crops and other industrial applications.

Synthesis of α-tocopherol-5-Me-D

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Corol, Delia; Mihaila, V.; Chiper, Diana

1999-01-01

Vitamin E is a group of eight different compounds having a methylate and hydroxylate oxygen ring condensed with a benzene molecule. Four of them, called tocopherols, have a saturated lateral chain deriving from phytol, while the tocotrienol compounds have the same chain and three double bonds. Vitamin E is essential for the reproduction process and intervenes in cellular oxidation processes, in muscular metabolism of creatinine and in carbon hydrate metabolism, facilitating the glycogen build-up in tissues. The labelling of vitamin E with deuterium is performed as follows: 1) Chloromethylation of γ-tocopherol to obtain α-tocopherol-5-Me-Cl; 2) Replacement of chlorine by deuterium in a dehalogenation catalytic reaction on Pd/C or Pd/CaCO 3 catalysts. The reaction scheme is given. The purification was performed by solvent selective extraction. The labelled compound characterization was carried out by NMR. (authors)

Controlled release of tocopherols from polymer blend films

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Obinata, Noe

Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies

Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

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Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

2014-01-01

Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

Neural control of colonic cell proliferation.

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Tutton, P J; Barkla, D H

1980-03-15

The mitotic rate in rat colonic crypts and in dimethylhydrazine-induced colonic carcinomas was measured using a stathmokinetic technique. In sympathectomized animals cell proliferation was retarded in the crypts but not in the tumors, whereas in animals treated with Metaraminol, a drug which releases norepinephrine from nerve terminals, crypt cell but not tumor cell proliferation was accelerated. Blockade of alpha-adrenoceptors also inhibited crypt cell proliferation. However, stimulation of beta-adrenoceptors inhibited and blockade of beta-adrenoceptors accelerated tumor cell proliferation without influencing crypt cell proliferation. Injection of either serotonin or histamine stimulated tumor but not crypt cell proliferation and blockade or serotonin receptors or histamine H2-receptors inhibited tumor cell proliferation. It is postulated that cell proliferation in the colonic crypts, like that in the jejunal crypts, is under both endocrine and autonomic neural control whereas colonic tumor cell division is subject to endocrine regulation alone.

Action of cholecalciferol and alpha-tocopherol on Staphylococcus aureus efflux pumps.

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Tintino, Saulo R; Morais-Tintino, Cícera D; Campina, Fábia F; Pereira, Raimundo L; Costa, Maria do S; Braga, Maria Flaviana B M; Limaverde, Paulo W; Andrade, Jacqueline C; Siqueira-Junior, José P; Coutinho, Henrique Douglas Melo; Balbino, Valdir Q; Leal-Balbino, Tereza C; Ribeiro-Filho, Jaime; Quintans-Júnior, Lucindo J

2016-01-01

Alpha-tocopherol is one the most abundant and biologically active isoforms of vitamin E. This compound is a potent antioxidant and one of most studied isoforms of vitamin E. Vitamin D3 (cholecalciferol) is an important nutrient for calcium homeostasis and bone health, that has also been recognized as a potent modulator of the immune response. Methicillin-resistant Staphylococcus aureus (MRSA) is the most important causative agent of both nosocomial and community-acquired infections. The aim of this study was to evaluate the inhibitory effect of alpha-tocopherol and cholecalciferol on both S. aureus and multidrug resistant S. aureus efflux pumps. The RN4220 strain has the plasmid pUL5054 that is the carrier of gene that encodes the macrolide resistance protein (an efflux pump) MsrA; the IS-58 strain possesses the TetK tetracycline efflux protein in its genome and the 1199B strain resists to hydrophilic fluoroquinolones via a NorA-mediated mechanism. The antibacterial activity was evaluated by determining the Minimal Inhibitory Concentration (MIC) and a possible inhibition of efflux pumps was associated to a reduction of the MIC. In this work we observed that in the presence of the treatments there was a decrease in the MIC for the RN4220 and IS-58 strains, suggesting that the substances presented an inhibitory effect on the efflux pumps of these strains. Significant efforts have been done to identify efflux pump inhibitors (EPIs) from natural sources and, therefore, the antibacterial properties of cholecalciferol and alpha-tocopherol might be attributed to a direct effect on the bacterial cell depending on their amphipathic structure.

Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal.

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Durnin, Leonie; Lees, Andrea; Manzoor, Sheerien; Sasse, Kent C; Sanders, Kenton M; Mutafova-Yambolieva, Violeta N

2017-11-01

Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα + ) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit W /Kit W-v ( W/W v ) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD + )/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5'-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/W v , Nos1 -/- , and Prkg1 -/- mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/W v mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/W v mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric

Unraveling the genetic basis of seed tocopherol content and composition in rapeseed (Brassica napus L.).

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Wang, Xingxing; Zhang, Chunyu; Li, Lingjuan; Fritsche, Steffi; Endrigkeit, Jessica; Zhang, Wenying; Long, Yan; Jung, Christian; Meng, Jinling

2012-01-01

Tocopherols are important antioxidants in vegetable oils; when present as vitamin E, tocopherols are an essential nutrient for humans and livestock. Rapeseed (Brassica napus L, AACC, 2 n = 38) is one of the most important oil crops and a major source of tocopherols. Although the tocopherol biosynthetic pathway has been well elucidated in the model photosynthetic organisms Arabidopsis thaliana and Synechocystis sp. PCC6803, knowledge about the genetic basis of tocopherol biosynthesis in seeds of rapeseed is scant. This project was carried out to dissect the genetic basis of seed tocopherol content and composition in rapeseed through quantitative trait loci (QTL) detection, genome-wide association analysis, and homologous gene mapping. We used a segregating Tapidor × Ningyou7 doubled haploid (TNDH) population, its reconstructed F(2) (RC-F(2)) population, and a panel of 142 rapeseed accessions (association panel). Genetic effects mainly contributed to phenotypic variations in tocopherol content and composition; environmental effects were also identified. Thirty-three unique QTL were detected for tocopherol content and composition in TNDH and RC-F(2) populations. Of these, seven QTL co-localized with candidate sequences associated with tocopherol biosynthesis through in silico and linkage mapping. Several near-isogenic lines carrying introgressions from the parent with higher tocopherol content showed highly increased tocopherol content compared with the recurrent parent. Genome-wide association analysis was performed with 142 B. napus accessions. Sixty-one loci were significantly associated with tocopherol content and composition, 11 of which were localized within the confidence intervals of tocopherol QTL. This joint QTL, candidate gene, and association mapping study sheds light on the genetic basis of seed tocopherol biosynthesis in rapeseed. The sequences presented here may be used for marker-assisted selection of oilseed rape lines with superior tocopherol

Unraveling the genetic basis of seed tocopherol content and composition in rapeseed (Brassica napus L..

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Xingxing Wang

Full Text Available BACKGROUND: Tocopherols are important antioxidants in vegetable oils; when present as vitamin E, tocopherols are an essential nutrient for humans and livestock. Rapeseed (Brassica napus L, AACC, 2 n = 38 is one of the most important oil crops and a major source of tocopherols. Although the tocopherol biosynthetic pathway has been well elucidated in the model photosynthetic organisms Arabidopsis thaliana and Synechocystis sp. PCC6803, knowledge about the genetic basis of tocopherol biosynthesis in seeds of rapeseed is scant. This project was carried out to dissect the genetic basis of seed tocopherol content and composition in rapeseed through quantitative trait loci (QTL detection, genome-wide association analysis, and homologous gene mapping. METHODOLOGY/PRINCIPAL FINDINGS: We used a segregating Tapidor × Ningyou7 doubled haploid (TNDH population, its reconstructed F(2 (RC-F(2 population, and a panel of 142 rapeseed accessions (association panel. Genetic effects mainly contributed to phenotypic variations in tocopherol content and composition; environmental effects were also identified. Thirty-three unique QTL were detected for tocopherol content and composition in TNDH and RC-F(2 populations. Of these, seven QTL co-localized with candidate sequences associated with tocopherol biosynthesis through in silico and linkage mapping. Several near-isogenic lines carrying introgressions from the parent with higher tocopherol content showed highly increased tocopherol content compared with the recurrent parent. Genome-wide association analysis was performed with 142 B. napus accessions. Sixty-one loci were significantly associated with tocopherol content and composition, 11 of which were localized within the confidence intervals of tocopherol QTL. CONCLUSIONS/SIGNIFICANCE: This joint QTL, candidate gene, and association mapping study sheds light on the genetic basis of seed tocopherol biosynthesis in rapeseed. The sequences presented here may be used

Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp transcription factors

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Pathi Satya

2011-08-01

Full Text Available Abstract Background Betulinic acid (BA inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS, ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent.

Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

International Nuclear Information System (INIS)

Chintharlapalli, Sudhakar; Papineni, Sabitha; Lei, Ping; Pathi, Satya; Safe, Stephen

2011-01-01

Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent

5-Geranyloxy-7-methoxycoumarin inhibits colon cancer (SW480) cells growth by inducing apoptosis.

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Patil, Jaiprakash R; Jayaprakasha, Guddadarangavvanahally K; Kim, Jinhee; Murthy, Kotamballi N Chidambara; Chetti, Mahadev B; Nam, Sang-Yong; Patil, Bhimanagouda S

2013-03-01

For the first time, three coumarins were isolated from the hexane extract of limes (Citrus aurantifolia) and purified by flash chromatography. The structures were identified by NMR (1D, 2D) and mass spectral analyses as 5-geranyloxy-7-methoxycoumarin, limettin, and isopimpinellin. These compounds inhibited human colon cancer (SW-480) cell proliferation, with 5-geranyloxy-7-methoxycoumarin showing the highest inhibition activity (67 %) at 25 µM. Suppression of SW480 cell proliferation by 5-geranyloxy-7-methoxycoumarin was associated with induction of apoptosis, as evidenced by annexin V staining and DNA fragmentation. In addition, 5-geranyloxy-7-methoxycoumarin arrested cells at the G0/G1 phase, and induction of apoptosis was demonstrated through the activation of tumour suppressor gene p53, caspase8/3, regulation of Bcl2, and inhibition of p38 MAPK phosphorylation. These findings suggest that 5-geranyloxy-7-methoxycoumarin has potential as a cancer preventive agent. Georg Thieme Verlag KG Stuttgart · New York.

Inhibition of Fungal Colonization by Pseudoalteromonas tunicata Provides a Competitive Advantage during Surface Colonization†

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Franks, A.; Egan, S.; Holmström, C.; James, S.; Lappin-Scott, H.; Kjelleberg, S.

2006-01-01

The marine epiphytic bacterium Pseudoalteromonas tunicata produces a range of extracellular secondary metabolites that inhibit an array of common fouling organisms, including fungi. In this study, we test the hypothesis that the ability to inhibit fungi provides P. tunicata with an advantage during colonization of a surface. Studies on a transposon-generated antifungal-deficient mutant of P. tunicata, FM3, indicated that a long-chain fatty acid-coenzyme A ligase is involved in the production of a broad-range antifungal compound by P. tunicata. Flow cell experiments demonstrated that production of an antifungal compound provided P. tunicata with a competitive advantage against a marine yeast isolate during surface colonization. This compound enabled P. tunicata to disrupt an already established fungal biofilm by decreasing the number of yeast cells attached to the surface by 66% ± 9%. For in vivo experiments, the wild-type and FM3 strains of P. tunicata were used to inoculate the surface of the green alga Ulva australis. Double-gradient denaturing gradient gel electrophoresis analysis revealed that after 48 h, the wild-type P. tunicata had outcompeted the surface-associated fungal community, whereas the antifungal-deficient mutant had no effect on the fungal community. Our data suggest that P. tunicata is an effective competitor against fungal surface communities in the marine environment. PMID:16957232

[Role of oral cavity colonization resistance in dental caries development].

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Petrushanko, T A; Chereda, V V; Loban', G A

2013-01-01

Colonization resistance is one of local immunity mechanisms determined by a combination of factors that inhibit the adhesion and growth of mucous membrane bacteria. We examined patients with different levels of caries intensity assessing oral mucosa colonization resistance by our own method. Caries development resulted in changes of colonization resistance with the increased rate of inhibition of the oral mucosa colonization resistance barrier.

GEN-27, a Newly Synthetic Isoflavonoid, Inhibits the Proliferation of Colon Cancer Cells in Inflammation Microenvironment by Suppressing NF-κB Pathway

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Yajing Wang

2016-01-01

Full Text Available Nonresolving inflammation is one of the consistent features of the tumor microenvironment in the intestine and plays a critical role in the initiation and development of colon cancer. Here we reported the inhibitory effects of GEN-27, a new derivative of genistein, on the inflammation-related colon cancer cell proliferation and delineated the mechanism of its action. The results indicated that GEN-27 inhibited the proliferation of human colon tumor HCT116 cells stimulated by culture supernatants of LPS-induced human monocytes THP-1 cells and significantly decreased LPS-induced secretion of proinflammatory cytokines interleukin-6 and interleukin-1β in THP-1 cells. The HCT116 cell proliferation elicited by THP-1-conditioned medium could be blocked by the interleukin-1 receptor antagonist (IL-1RA. Further mechanistic study revealed that GEN-27 remarkably inhibited the nuclear translocation of NF-κB and phosphorylation of IκB and IKKα/β in both HCT116 and THP-1 cells. In addition, GEN-27 markedly suppressed the HCT116 cell proliferation stimulated by IL-1β treatment, which was dependent on the inhibition of NF-κB/p65 nuclear localization, as verified by p65 overexpression and BAY 11-7082, an NF-κB inhibitor. Taken together, our findings established that GEN-27 modulated NF-κB signaling pathway involved in inflammation-induced cancer cells proliferation and therefore could be a potential chemopreventive agent against inflammation-associated colon cancer.

GEN-27, a Newly Synthetic Isoflavonoid, Inhibits the Proliferation of Colon Cancer Cells in Inflammation Microenvironment by Suppressing NF-κB Pathway.

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Wang, Yajing; Lu, Ping; Zhang, Weifeng; Du, Qianming; Tang, Jingjing; Wang, Hong; Lu, Jinrong; Hu, Rong

2016-01-01

Nonresolving inflammation is one of the consistent features of the tumor microenvironment in the intestine and plays a critical role in the initiation and development of colon cancer. Here we reported the inhibitory effects of GEN-27, a new derivative of genistein, on the inflammation-related colon cancer cell proliferation and delineated the mechanism of its action. The results indicated that GEN-27 inhibited the proliferation of human colon tumor HCT116 cells stimulated by culture supernatants of LPS-induced human monocytes THP-1 cells and significantly decreased LPS-induced secretion of proinflammatory cytokines interleukin-6 and interleukin-1β in THP-1 cells. The HCT116 cell proliferation elicited by THP-1-conditioned medium could be blocked by the interleukin-1 receptor antagonist (IL-1RA). Further mechanistic study revealed that GEN-27 remarkably inhibited the nuclear translocation of NF-κB and phosphorylation of IκB and IKKα/β in both HCT116 and THP-1 cells. In addition, GEN-27 markedly suppressed the HCT116 cell proliferation stimulated by IL-1β treatment, which was dependent on the inhibition of NF-κB/p65 nuclear localization, as verified by p65 overexpression and BAY 11-7082, an NF-κB inhibitor. Taken together, our findings established that GEN-27 modulated NF-κB signaling pathway involved in inflammation-induced cancer cells proliferation and therefore could be a potential chemopreventive agent against inflammation-associated colon cancer.

γ-Aminobutyric acid inhibits the proliferation and increases oxaliplatin sensitivity in human colon cancer cells.

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Song, Lihua; Du, Aiying; Xiong, Ying; Jiang, Jing; Zhang, Yao; Tian, Zhaofeng; Yan, Hongli

2016-11-01

γ-Aminobutyric acid (GABA) is a natural non-protein amino acid, which broadly exists in many plant parts and is widely used as an ingredient in the food industry. In mammals, it is widely distributed in central nervous system and non-neural tissues. In addition to a primary inhibitory neurotransmitter in the central nervous system, endogenous GABA content has been found to be elevated in neoplastic tissues in colon cancer. However, the effect of extraneous GABA on colon cancer has rarely been reported. In this study, we found the inhibitory effects of GABA on the proliferation of colon cancer cells (CCCs). The amino acid also suppressed metastasis of SW480 and SW620 cells. To further study the correlated mechanism, we analyzed the changes in cell cycle distribution and found that GABA suppressed cell cycle progression through G2/M or G1/S phase. Furthermore, RNA sequencing analysis revealed GABA-induced changes in the mRNA expression of 30 genes, including EGR1, MAPK4, NR4A1, Fos, and FosB, in all the three types of CCC. Importantly, GABA enhanced the anti-tumor efficacy of oxaliplatin (OXA) in subcutaneous xenograft tumor model in nude mice. The data suggest that GABA inhibits colon cancer cell proliferation perhaps by attenuating EGR1-NR4A1 axis, EGR1-Fos axis, and by disrupting MEK-EGR1 signaling pathway. This work reveals the pharmacological value of GABA derived from food and suggests that exogenous GABA might play an auxiliary role in polychemotherapy of colon cancer.

α-Tocopherol-5-Me-D synthesis, purification and characterization

International Nuclear Information System (INIS)

Corol-Cucu, Delia-Irina; Chiper, Diana; Mihaila, V.; Negoita, N.

2000-01-01

Vitamine E contains eight different compounds which have a ring with methyl and hydroxyl groups. Four of them, named tocopherols, contain a lateral saturated chain which derives from fitol and the others, named tocotrienols, have three double bounds in the lateral chain. The E vitamine is named 'vitamine of antisterility' because it is essential for good functioning of genital organs. It is involved in cellular oxidation processes, in muscle creatinine metabolism and metabolism of saccharides encouraging glycogen deposition in tissues. The labelling with deuterium of E vitamine is done in the following way: - The synthesis of α-tocopherol-5-Me-Cl from γ-tocopherol; - The replacement of chlorine with deuterium through catalytic dechlorination reaction. One obtains α-tocopherol-5-Me-D. The purification has been carried out through thin layer preparative chromatography, with C 6 H 6 as solvent (Al 2 O 3 as support) or solvent system C 6 H 6 :CH 3 OH (98:2, v/v) (silicagel as support). (authors)

Quantification of minerals and tocopherols isomers in chestnuts approach chemometrics

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Nilson Evelazio de Souza

2014-10-01

Full Text Available The levels of the ?, ?, and (?+?-tocopherol isomers and the amounts of the minerals Se, Zn, Ca, Fe, K, Mn, Mg, and Cu were analyzed in chestnuts. High contents of Zn (>65% relative to the recommended dietary intake (RDI were found in all chestnuts except macadamia nuts (25% of the RDI. All samples had Se contents higher than the RDI: Brazil nuts > macadamia nuts, cashew nuts > pecans > almonds > pistachio nuts > hazelnuts > European nuts. A greater concentration of ?-tocopherol was found in almonds (30% of RDI. All samples, except for hazelnuts, almonds, and macadamia nuts, had (?+?- tocopherols, with the largest amount found in pistachios. Only pecan nuts and European nuts had ?-tocopherol and only in low amounts. Multivariate analysis allowed for better characterization and distinction of the chestnuts

A Comparison of Natural (D-α-tocopherol) and Synthetic (DL-α-tocopherol Acetate) Vitamin E Supplementation on the Growth Performance, Meat Quality and Oxidative Status of Broilers.

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Cheng, K; Niu, Y; Zheng, X C; Zhang, H; Chen, Y P; Zhang, M; Huang, X X; Zhang, L L; Zhou, Y M; Wang, T

2016-05-01

The present study was conducted to compare the supplementation of natural (D-α-tocopherol) and synthetic (DL-α-tocopherol acetate) vitamin E on the growth performance, meat quality, muscular antioxidant capacity and genes expression related to oxidative status of broilers. A total of 144 1 day-old Arbor Acres broiler chicks were randomly allocated into 3 groups with 6 replicates of 8 birds each. Birds were given a basal diet (control group), and basal diet supplemented with either 20 IU D-α-tocopherol or DL-α-tocopherol acetate for 42 days, respectively. The results indicated that treatments did not alter growth performance of broilers (p>0.05). Compared with the control group, concentration of α-tocopherol in the breast muscle was increased by the supplementation of vitamin E (pnatural vitamin E group (pnatural vitamin E group (pnatural rather than synthetic vitamin E reduced MDA accumulation in the thigh (pnatural nor synthetic vitamin E supplementation altered muscular mRNA abundance of genes related to oxidative stress (p>0.05). It was concluded that vitamin E supplementation, especially the natural vitamin E, can enhance the retention of muscular α-tocopherol, improve meat quality and muscular antioxidant capacity of broilers.

Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

LENUS (Irish Health Repository)

Alzamora, Rodrigo

2011-01-01

Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 ± 8 μM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCα and PKA, but had no effect on p42\\/p44 MAPK and PKCδ. However, berberine pre-treatment prevented stimulation of p42\\/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE (∼65%), an inhibitor of PKCα and to a smaller extent by inhibition of p38 MAPK with SB202190 (∼15%). Berberine treatment induced an increase in association between PKCα and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCα-dependent pathway.

Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

LENUS (Irish Health Repository)

Alzamora, Rodrigo

2012-02-01

Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 +\\/- 8 muM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCalpha and PKA, but had no effect on p42\\/p44 MAPK and PKCdelta. However, berberine pre-treatment prevented stimulation of p42\\/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE ( approximately 65%), an inhibitor of PKCalpha and to a smaller extent by inhibition of p38 MAPK with SB202190 ( approximately 15%). Berberine treatment induced an increase in association between PKCalpha and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCalpha-dependent pathway.

Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.

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Romano, Barbara; Borrelli, Francesca; Pagano, Ester; Cascio, Maria Grazia; Pertwee, Roger G; Izzo, Angelo A

2014-04-15

Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. Proliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [(3)H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice. CBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer. CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients. Copyright © 2013 Elsevier GmbH. All rights reserved.

Combination of capecitabine and ludartin inhibits colon cancer ...

African Journals Online (AJOL)

Methods: Mice model of colon cancer was used in this study. Quantitative ... mRNA. Micro-vessel density was assessed using immunohistochemical analysis. ... increase in white blood cell (WBC) count, and increased median survival time of colon cancer mice from ..... tumor cells is associated with the development of.

A candidate gene-based association study of tocopherol content and composition in rapeseed (Brassica napus

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Steffi eFritsche

2012-06-01

Full Text Available Rapeseed (Brassica napus L. is the most important oil crop of temperate climates. Rapeseed oil contains tocopherols, also known as vitamin E, which is an indispensable nutrient for humans and animals due to its antioxidant and radical scavenging abilities. Moreover, tocopherols are also important for the oxidative stability of vegetable oils. Therefore, seed oil with increased tocopherol content or altered tocopherol composition is a target for breeding. We investigated the role of nucleotide variations within candidate genes from the tocopherol biosynthesis pathway. Field trials were carried out with 229 accessions from a worldwide B. napus collection which was divided into two panels of 96 and 133 accessions. Seed tocopherol content and composition were measured by HPLC. High heritabilities were found for both traits, ranging from 0.62 to 0.94. We identified polymorphisms by sequencing selected regions of the tocopherol genes from the 96 accession panel. Subsequently, we determined the population structure (Q and relative kinship (K as detected by genotyping with genome-wide distributed SSR markers. Association studies were performed using two models, the structure-based GLM+Q and the PK mixed model. Between 26 and 12 polymorphisms within two genes (BnaX.VTE3.a, BnaA.PDS1.c were significantly associated with tocopherol traits. The SNPs explained up to 16.93 % of the genetic variance for tocopherol composition and up to 10.48 % for total tocopherol content. Based on the sequence information we designed CAPS markers for genotyping the 133 accessions from the 2nd panel. Significant associations with various tocopherol traits confirmed the results from the first experiment. We demonstrate that the polymorphisms within the tocopherol genes clearly impact tocopherol content and composition in B. napus seeds. We suggest that these nucleotide variations may be used as selectable markers for breeding rapeseed with enhanced tocopherol quality.

Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway.

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Lakhan, Ram; Said, Hamid M

2017-04-01

Biotin (vitamin B7), an essential micronutrient for normal cellular functions, is obtained from both dietary sources as well as gut microbiota. Absorption of biotin in both the small and large intestine is via a carrier-mediated process that involves the sodium-dependent multivitamin transporter (SMVT). Although different physiological and molecular aspects of intestinal biotin uptake have been delineated, nothing is known about the effect of LPS on the process. We addressed this issue using in vitro (human colonic epithelial NCM460 cells) and in vivo (mice) models of LPS exposure. Treating NCM460 cells with LPS was found to lead to a significant inhibition in carrier-mediated biotin uptake. Similarly, administration of LPS to mice led to a significant inhibition in biotin uptake by native colonic tissue. Although no changes in total cellular SMVT protein and mRNA levels were observed, LPS caused a decrease in the fraction of SMVT expressed at the cell surface. A role for casein kinase 2 (CK2) (whose activity was also inhibited by LPS) in mediating the endotoxin effects on biotin uptake and on membrane expression of SMVT was suggested by findings that specific inhibitors of CK2, as well as mutating the putative CK2 phosphorylation site (Thr 78 Ala) in the SMVT protein, led to inhibition in biotin uptake and membrane expression of SMVT. This study shows for the first time that LPS inhibits colonic biotin uptake via decreasing membrane expression of its transporter and that these effects likely involve a CK2-mediated pathway.

Methylselenol, a selenium metabolite, modulates p53 pathway and inhibits the growth of colon cancer xenografts in Balb/c mice.

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Zeng, Huawei; Cheng, Wen-Hsing; Johnson, Luann K

2013-05-01

It is has been hypothesized that methylselenol is a critical selenium metabolite for anticancer activity in vivo. In this study, we used a protein array which contained 112 different antibodies known to be involved in the p53 pathway to investigate the molecular targets of methylselenol in human HCT116 colon cancer cells. The array analysis indicated that methylselenol exposure changed the expression of 11 protein targets related to the regulation of cell cycle and apoptosis. Subsequently, we confirmed these proteins with the Western blotting approach, and found that methylselenol increased the expression of GADD 153 and p21 but reduced the level of c-Myc, E2F1 and Phos p38 MAP kinase. Similar to our previous report on human HCT116 colon cancer cells, methylselenol also inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase in mouse colon cancer MC26 cells. When the MC26 cells were transplanted to their immune-competent Balb/c mice, methylselenol-treated MC26 cells had significantly less tumor growth potential than that of untreated MC26 cells. Taken together, our data suggest that methylselenol modulates the expression of key genes related to cell cycle and apoptosis and inhibits colon cancer cell proliferation and tumor growth. Copyright © 2013. Published by Elsevier Inc.

Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis

International Nuclear Information System (INIS)

Hille, A.; Christiansen, H.; Pradier, O.; Hermann, R.M.; Siekmeyer, B.; Weiss, E.; Hess, C.F.; Schmidberger, H.; Hilgers, R.

2005-01-01

Background and purpose: Chronic radiation proctitis/enteritis is a relevant complication of pelvic irradiation, which is still mainly treated by supportive measures only. There is some evidence that the combined treatment with pentoxifylline and tocopherol might alter the pathogenesis of radiation-induced fibrosis. In a retrospective analysis the clinical benefit of the treatment with pentoxifylline/tocopherol on radiation-induced proctitis/enteritis was evaluated, compared to supportive care only. Patients and methods: Of 30 patients with radiation-induced proctitis/enteritis grade I-II according to the RTOG/EORTC toxicity criteria, 21 were treated with pentoxifylline and tocopherol. Depending on physician's decision nine patients received symptomatic treatment only. Results: With pentoxifylline/tocopherol treatment 15/21 patients (71%) experienced a relief of their symptoms. A reduction from grade I/II to grade 0 toxicity was observed in seven and from grade II to grade I toxicity in eight patients. No improvement was seen in six patients. The median time to improvement with pentoxifylline and tocopherol treatment was 28 weeks. In three of nine patients who were treated supportively only, deterioration of symptoms occurred. Three patients experienced no amelioration, and three patients with grade I toxicity experienced a spontaneous relief of their symptoms (33%). Conclusion: The combination treatment with pentoxifylline and tocopherol seems to have a benefit in patients with grade I-II radiation-induced proctitis/enteritis. The optimal schedule of treatment duration is not yet clear. From the observations made in this study it is assumed the treatment should be given for 6-12 months at least. A prospective phase II study should be undertaken to evaluate optimal treatment duration. (orig.)

Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis

Energy Technology Data Exchange (ETDEWEB)

Hille, A.; Christiansen, H.; Pradier, O.; Hermann, R.M.; Siekmeyer, B.; Weiss, E.; Hess, C.F.; Schmidberger, H. [Goettingen Univ. (Germany). Dept. of Radiotherapy and Radiation; Hilgers, R. [Goettingen Univ. (Germany). Dept. for Medical Statisics

2005-09-15

Background and purpose: Chronic radiation proctitis/enteritis is a relevant complication of pelvic irradiation, which is still mainly treated by supportive measures only. There is some evidence that the combined treatment with pentoxifylline and tocopherol might alter the pathogenesis of radiation-induced fibrosis. In a retrospective analysis the clinical benefit of the treatment with pentoxifylline/tocopherol on radiation-induced proctitis/enteritis was evaluated, compared to supportive care only. Patients and methods: Of 30 patients with radiation-induced proctitis/enteritis grade I-II according to the RTOG/EORTC toxicity criteria, 21 were treated with pentoxifylline and tocopherol. Depending on physician's decision nine patients received symptomatic treatment only. Results: With pentoxifylline/tocopherol treatment 15/21 patients (71%) experienced a relief of their symptoms. A reduction from grade I/II to grade 0 toxicity was observed in seven and from grade II to grade I toxicity in eight patients. No improvement was seen in six patients. The median time to improvement with pentoxifylline and tocopherol treatment was 28 weeks. In three of nine patients who were treated supportively only, deterioration of symptoms occurred. Three patients experienced no amelioration, and three patients with grade I toxicity experienced a spontaneous relief of their symptoms (33%). Conclusion: The combination treatment with pentoxifylline and tocopherol seems to have a benefit in patients with grade I-II radiation-induced proctitis/enteritis. The optimal schedule of treatment duration is not yet clear. From the observations made in this study it is assumed the treatment should be given for 6-12 months at least. A prospective phase II study should be undertaken to evaluate optimal treatment duration. (orig.)

[6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling.

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E K Radhakrishnan

Full Text Available We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale, in colon cancer cells. The compound was evaluated in two human colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-gingerol in SW-480 cells was associated with activation of caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-gingerol down-regulated Phorbol Myristate Acetate (PMA induced phosphorylation of ERK1/2 and JNK MAP kinases and activation of AP-1 transcription factor, but had only little effects on phosphorylation of p38 MAP kinase and activation of NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-gingerol against colon cancer.

Alkaline saponification results in decomposition of tocopherols in milk and ovine blood plasma.

Science.gov (United States)

Czauderna, M; Kowalczyk, J

2007-10-15

Alkaline saponification of entire sample matrixes for quantification of alpha-, gamma-, delta-tocopherols (alpha-T, gamma-T, delta-T) and alpha-tocopherol acetate (alpha-TAc) was examined. High-performance liquid chromatography was used to measure alpha-T, gamma-T, delta-T and alpha-TAc in tocopherol standard solutions, milk and ovine blood plasma. Saponification in the presence of vitamin C decreases the concentration of tocopherols, especially alpha-T and gamma-T. The poor recovery of tocopherols is due to the decomposition of tocopherols in saponified standard solutions, milk or plasma. Saponification of samples in the presence of 2,[6]-ditertbutyl-p-cresol or flushed only with a stream of Ar resulted in a major decrease in the concentrations of alpha-T, gamma-T, delta-T and alpha-TAc in comparison with saponification in the presence of vitamin C.

Effect of dietary alpha-tocopherol supplementation and gamma-irradiation on alpha-tocopherol retention and lipid oxidation in cooked minced chicken

International Nuclear Information System (INIS)

Galvin, K.; Morrissey, P.A.; Buckley, D.J.

1998-01-01

The effects of dietary alpha-tocopherol supplementation and gamma-irradiation on alpha-tocopherol retention and lipid oxidation in cooked minced chicken during refrigerated storage were studied. Minced breast and thigh meat from broilers fed diets supplemented with 100, 200 or 400 mg alpha-tocopheryl acetate/kg feed was irradiated at 2.5 or 4.0 kGy. Cooked irradiated and unirradiated meat was stored at 4 degrees C for 5 days. alpha-Tocopherol concentrations increased with increasing dietary supplementation. Concentrations decreased during storage, but retention was not affected by irradiation. Lipid stability was determined by measuring the formation of thiobarbituric acid-reacting substances (TBARS) and cholesterol oxidation products (COPs) during storage. TBARS and COPs increased during storage and were reduced by increasing levels of dietary alpha-tocopheryl acetate supplementation. Irradiation accelerated TBARS formation during storage, but this was prevented by supplementation with 200 mg alpha-tocopheryl acetate/kg feed. Irradiation tended to increase COPs during storage, although no consistent effects were observed. In general supplementation with over 400 mg alpha-tocopheryl acetate/kg feed may be required to control cholesterol oxidation in minced chicken. The results suggest that, overall, irradiation had little effect on lipid stability in alpha-tocopherol-supplemented meat following cooking and storage

Combination of capecitabine and ludartin inhibits colon cancer ...

African Journals Online (AJOL)

Purpose: To investigate the efficacy of capecitabine and ludartin in the treatment of colon cancer in mice. Methods: Mice model of colon cancer was used in this study. Quantitative real-time polymerase chain reaction (Qrt-PCR) was used to quantify the expression of vascular endothelial growth factor (VEGF) mRNA.

Inositol Hexaphosphate Inhibits Proliferation and Induces Apoptosis of Colon Cancer Cells by Suppressing the AKT/mTOR Signaling Pathway

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Małgorzata Kapral

2017-10-01

Full Text Available Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as an attractive target for anticancer therapy. Inositol hexaphosphate (InsP6, a natural occurring phytochemical, has been shown to have both preventive and therapeutic effects against various cancers, however, its exact molecular mechanisms of action are not fully understood. The aim of the in vitro study was to investigate the anticancer activity of InsP6 on colon cancer with the focus on inhibiting the AKT1 kinase and p70S6K1 as mTOR effector, in relation to proliferation and apoptosis of cells. The colon cancer Caco-2 cells were cultured using standard techniques and exposed to InsP6 at different concentrations (1 mM, 2.5 mM and 5 mM. Cellular proliferative activity was monitored by 5-bromo-2′-deoxyuridine (BrdU incorporation into cellular DNA. Flow cytometric analysis was performed for cell cycle progression and apoptosis studies. Real-time RT-qPCR was used to validate mRNA levels of CDNK1A, CDNK1B, CASP3, CASP9, AKT1 and S6K1 genes. The concentration of p21 protein as well as the activities of caspase 3, AKT1 and p70S6K1 were determined by the ELISA method. The results revealed that IP6 inhibited proliferation and stimulated apoptosis of colon cancer cells. This effect was mediated by an increase in the expression of genes encoding p21, p27, caspase 3, caspase 9 as well a decrease in transcription of AKT1 and S6K1. InsP6 suppressed phosphorylation of AKT1 and p70S6K1, downstream effector of mTOR. Based on these studies it may be concluded that InsP6 can reduce proliferation and induce apoptosis through inhibition of the AKT/mTOR pathway and mTOR effector followed by modulation of the expression and activity of several key components of these pathways in

Modification of survival and hematopoiesis in mice by tocopherol injection following irradiation

International Nuclear Information System (INIS)

Bichay, T.J.E.; Roy, R.M.

1986-01-01

The LD 50/30 of CD-1-female mice increased from 6.6 Gy to 7.0 Gy when 2.5 mg of dl-α-tocopherol was injected immediately post irradiation. Increased survival was associated with increased numbers of hematopoietic colony forming units (CFU). Endogeneous spleen colonies were found in greater numbers in the tocopherol-treated mice after irradiation. The vitamin, however, must be injected within five hours following irradiation to have this effect. The increased numbers of CFU in tocopherol-treated mice may be due to a stimulation of recovery of repair processes. Split-dose studies suggest that most repair of sublethal damage in hematopoietic stem cells take place within seven and nine hours following irradiation. Tocopherol injection appears to enhance the recovery manifested in the split-dose assay. There is also evidence that tocopherol-treatment caused an earlier onset of mitotic activity in CFU after irradiation. The increased number of spleen colonies in tocopherol-injected mice is not due to an altered CFU seeding efficiency associated with an altered spleen microenvironment. Tocopherol injection did not affect the shoulder of the stem cell survival curve using exogenous spleen colony assays of bone marrow-derived or spleen-derived hematopoietic stem cells. There appears to be a decrease in D 0 in the higher dose region (4.3 Gy) of the bone marrow exogenous SCA survival curves for the vehicle-injected and the non-injected groups; however, the tocopherol-injected group showed no evidence of change in radiosensitivity up to the highest dose used (5.0 Gy). Data may be interpreted to suggest that the therapeutic effect of tocopherol may involve repair of hematopoietic stem cell damage in the higher dose range of bone marrow syndrome. (orig.) [de

Functions of tocopherols in the cells of plants and other photosynthetic organisms.

Science.gov (United States)

Mokrosnop, V M

2014-01-01

Tocopherol synthesis has only been observed in photosynthetic organisms (plants, algae and some cyanobacteria). Tocopherol is synthesized in the inner membrane of chloroplasts and distributed between chloroplast membranes, thylakoids and plastoglobules. Physiological significance of tocopherols for human and animal is well-studied, but relatively little is known about their function in plant organisms. Among the best characterized functions oftocopherols in cells is their ability to scavenge and quench reactive oxygen species and fat-soluble by-products of oxidative stress. There are the data on the participation of different mechanisms of α-tocopherol action in protecting photosystem II (PS II) from photoinhibition both by deactivation of singlet oxygen produced by PSII and by reduction of proton permeability of thylakoid membranes, leading to acidification of lumen under high light conditions and activation of violaxanthin de-epoxidase. Additional biological activity of tocopherols, independent of its antioxidant functions have been demonstrated. Basic mechanisms for these effects are connected with the modulation of signal transduction pathways by specific tocopherols and, in some instances, by transcriptional activation of gene expression.

Syntheses of α and γ-tocopherols selectively labelled with deuterium

International Nuclear Information System (INIS)

Hughes, L.; Slaby, M.; Burton, G.W.; Ingold, K.U.

1990-01-01

Four deuterium-substituted α-tocopherols (dideutero-RRR, nonadeutero-ambo, nonadeutero-all-rac and undecadeutero-all-rac) and a dideutro-RRR-γ-tocopherol have been synthesized for use in studies of the biokinetics, bioavailability and metabolism of vitamin E. (author)

E-selectin: sialyl Lewis, a dependent adhesion of colon cancer cells, is inhibited differently by antibodies against E-selectin ligands.

Science.gov (United States)

Srinivas, U; Påhlsson, P; Lundblad, A

1996-09-01

Recent studies have demonstrated that selectins, a new family of cell-adhesion molecules with similar domain structures, mediate the adhesion of peripheral blood cells to interleukin-1 (IL-1)-activated endothelium. In the present study the authors evaluated the role of E-selectin-Sialyl Lewis x (SLe(x))/ Sialyl Lewis a (SLe(a)) interaction in mediating in vitro adhesion of two colon cancer cell lines, HT-29 and COLO 201, to human umbilical cord endothelial cells (HUVEC). Colon cancer cell lines had a strong expression of blood group-related carbohydrate epitopes as evaluated by fluorescence-activated cell sorter (FACS) analysis. It was established that adhesion of HT-29 and COLO 201 cells to IL-1 stimulated HUVEC was calcium dependent and could be inhibited by a monoclonal antibody directed against E-selectin. Prior incubation of cells with two different antibodies directed against SLe(x) and antibodies directed against related Lewis epitopes, Le(x) and Le(a), had no significant effect on adhesion. Three antibodies directed against SLe(a) differed in their capacity to inhibit the adhesion of HT-29 and COLO 201 cells to HUVEC. Only one antibody directed against the SLe(a) structure was effective in inhibiting adhesion of both COLO 201 and HT-29 cells. The difference could not be attributed to titre, the type or number of glycoproteins, or to a difference in the amount of SLe(a) present on individual proteins, suggesting that presence and right presentation of SLe(a) epitope might be important for adhesion of colon cancer cells. Finally, in the in vitro system used, adhesion of HT-29 and COLO 201 cells to activated HUVEC is mediated predominantly by E-selectin/SLe(a) interaction. SLe(x) and related epitopes, Le(x) and Le(a), seem to have limited relevance for colon cancer cell recognition of E-selectin.

[Effect of nonsteroidal antiinflammatory drugs on colonic lipoxygenase and cyclooxygenase activities from patients with colonic neoplasia].

Science.gov (United States)

Di Girolamo, G; Franchi, A; De Los Santos, A R; Martí, M L; Farina, M; Fernández de Gimeno, M A

2001-01-01

Lysine clonixinate (LC) is a nonsteroidal anti-inflammatory drug (NSAID) with good gastrointestinal tolerance. Treatment with LC at levels equivalent to those found in plasma following therapeutic doses resulted in significant inhibition of both cyclooxygenase 2 (COX-2) and production of 5 hydroxy-eicosatetraeonic acid (5-HETE) and slightly affected levels of cyclooxygenase 1 (COX-1) in in vitro studies carried out on human tissues. This study deals with the in vivo effect of the drug on human colon segments. Experiment 1: Five patients about to undergo hemicholectomy due to colon neoplasia were treated preoperatively with a continuous infusion of LC, to achieve a steady-state concentration between 4 and 6 mg/ml. Human colon segments from the five patients and from another five control patients receiving no treatment with [14C]-arachidonic acid were incubated. Human colon segments treated with LC showed significant inhibition of PGE2, the only prostaglandin (PG) synthesised by the tissue, as well as of 5-HETE. Experiment 2: Fifteen patients received an i.v. bolus of LC 100 mg (n1 = 5); LC 200 mg (n2 = 5) or indomethacin (INDO) 50 mg (n3 = 5). Both doses of LC showed greater inhibition of PGE2 synthesis than the INDO bolus. Both NSAIDs studied proved to have different effects on the production of 5-HETE; while treatment with LC elicited significant inhibition, levels with INDO remained unchanged. Western blotting analysis showed expression of both COX isoforms in colon segments, COX-2 levels being 20% higher. Both types of in vivo studies conducted continuous infusion and i.v. bolus, revealed that LC exerted significant inhibition of basal synthesis of PGE2 and 5-HETE.

Genetic disruption of tubulin acetyltransferase, αTAT1, inhibits proliferation and invasion of colon cancer cells through decreases in Wnt1/β-catenin signaling

International Nuclear Information System (INIS)

Oh, Somi; You, Eunae; Ko, Panseon; Jeong, Jangho; Keum, Seula; Rhee, Sangmyung

2017-01-01

Microtubules are required for diverse cellular processes, and abnormal regulation of microtubule dynamics is closely associated with severe diseases including malignant tumors. In this study, we report that α-tubulin N-acetyltransferase (αTAT1), a regulator of α-tubulin acetylation, is required for colon cancer proliferation and invasion via regulation of Wnt1 and its downstream genes expression. Public transcriptome analysis showed that expression of ATAT1 is specifically upregulated in colon cancer tissue. A knockout (KO) of ATAT1 in the HCT116 colon cancer cell line, using the CRISPR/Cas9 system showed profound inhibition of proliferative and invasive activities of these cancer cells. Overexpression of αTAT1 or the acetyl-mimic K40Q α-tubulin mutant in αTAT1 KO cells restored the invasiveness, indicating that microtubule acetylation induced by αTAT1 is critical for HCT116 cell invasion. Analysis of colon cancer-related gene expression in αTAT1 KO cells revealed that the loss of αTAT1 decreased the expression of WNT1. Mechanistically, abrogation of tubulin acetylation by αTAT1 knockout inhibited localization of β-catenin to the plasma membrane and nucleus, thereby resulting in the downregulation of Wnt1 and of its downstream genes including CCND1, MMP-2, and MMP-9. These results suggest that αTAT1-mediated Wnt1 expression via microtubule acetylation is important for colon cancer progression. - Highlights: • Ablation of αTAT1 inhibits HCT116 colon cancer cell invasion. • αTAT1/acetylated microtubules regulate expression of Wnt1/β-catenin target genes. • Acetylated microtubules regulate cellular localization of β-catenin. • Loss of αTAT1 prevents Wnt1 from inducing β-catenin-dependent and -independent pathways.

Pharmacological dose of alpha-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

Science.gov (United States)

The effect of pharmacological dose of alpha-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha-tocopherol, n = 11) group. Animals received corn oil (C) or alpha-tocopherol dissolved in corn oil (250 mg alpha-tocopherol/[...

Effect of tocopherol on atherosclerosis, vascular function, and inflammation in apolipoprotein E knockout mice with subtotal nephrectomy.

Science.gov (United States)

Shing, Cecilia M; Fassett, Robert G; Peake, Jonathan M; Coombes, Jeff S

2014-12-01

Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E(-/-) mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease. Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol). Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10(-7) M to 3 × 10(-5) M (P tocopherol reduced systemic concentrations of IL-6 (P tocopherol also reduced MCP-1 (P tocopherol supplementation when compared to normal chow (P Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E(-/-) mouse with CKD. © 2014 John Wiley & Sons Ltd.

Increased haematopoietic stem cell survival in mice injected with tocopherol after X-irradiation

International Nuclear Information System (INIS)

Roy, R.M.; Malick, M.A.; Clark, G.M.

1982-01-01

Tocopherol injection (2.5 mg) immediately after irradiation reduced lethality only during bone-marrow syndrome. Endogenous spleen colony count at 8 days after X-radiation were significantly greater in vitamin-E-injected mice compared to noninjected or vehicle-injected animals; however, 59 Fe incorporation into spleen and bone marrow did not suggest enhanced erythropoietic activity in vitamin-E-injected groups at 2, 4, 8 and 10 days following irradiation. Mitotic index and frequency of micronuclei in marrow at 24 hours post irradiation (3 GY) were unaffected by tocopherol injection. The uptake of tritium from injected 3 H-tocopherol suggests that tocopherol has been accumulated in spleens but not marrows of irradiated animals within a few hours. Also tocopherol has no effect on endogenous spleen colony counts if injected after 5 hours nor is there an effect on the seeding efficiency of exogenous bonemarrow cells injected into recipients receiving tocopherol after irradiation. (orig.) [de

An Insight into the Interactions between a-Tocopherol and Chitosan in Ultrasound-Prepared Nanoparticles

International Nuclear Information System (INIS)

Naghibzadeh, M.; Amani, A.; Esmaeilzadeh, E.; Amini, M.; Mottaghi-Dastjerdi, N.; Faramarzi, M.A.; Faramarzi, M.A.

2010-01-01

The aim of this study was to investigate the interactions between a-tocopherol and chitosan molecules prepared subsequent to preparation of a-tocopherol-loaded chitosan nanoparticles using ultrasonication. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) analyses showed semi spherical particles with an average size of approximately 350 nm. Also from reconstitution test, a-tocopherol was suggested as stabilizing agent during lyophilization/reconstitution process. The zeta potentials of chitosan and a-tocopherol nanoparticles were larger than ±30 mV, representing suitable stability. Data obtained from FTIR showed possibility of chemical interaction between chitosan and a-tocopherol. Furthermore, the results from FTIR, NMR, and XRD spectroscopy confirmed electrostatic interactions between the two molecules. Overall, this procedure could be considered as a facile method to prepare a-tocopherol-loaded nanoparticles.

Den tilsatte mængde α-tocopherol til minkfoder kan reduceres

DEFF Research Database (Denmark)

Hymøller, Lone; Clausen, Tove N.; Clausen, Ditte

2016-01-01

Behovet for -Tocopherol (vitamin E) hos mink var tidligere vurderet til at være meget højt. Årsagen var minkfoderets høje indhold af letfordærvelige råvarer og indhold af fedt. Fedt harskner let, hvis det ikke opbevares under optimale temperatur- og iltmæssige forhold. -Tocopherol virker som...... transport af råvarer og færdigblandet foder. Dette gælder alle led af foderkæden såvel i foderindustri som på minkfarmene. Derfor er det rimeligt at genoverveje tidligere anbefalinger for -tocopherol i minkfoder med henblik på at vurdere behovet under moderne produktionsforhold og undgå en uøkonomisk...... overforsyning med -tocopherol. Forsøg gennemført i vækst- og pelsningssæsonen 2014 og 2015 med varierende tildeling af syntetisk og naturligt -tocopherol har vist, at de nuværende anbefalinger for -tocopheroltilsætning til minkfoder på 60 til 80 mg/kg foder kan reduceres til ca. 40 mg/kg foder, hvis der...

Glutathione delays varies as-tocopherol oxidation and subsequent lipid peroxidation in rat liver microsomes

International Nuclear Information System (INIS)

Robey, S.; Mavis, R.

1986-01-01

A method has been developed for in vitro trace radiolabeling of rat liver microsomes with 3 H-α-tocopherol (αT*) which allows virtually complete oxidation of the αT* under oxidizing conditions. The supernatant of a 16,000 xg centrifugation of homogenized rat liver, containing the cytosolic rat liver vitamin E (VE) transfer protein, was incubated with an ethanolic solution of αT* for 10 minutes at 37 0 C. Labeled microsomes were collected in the washed 100,000 xg pellet. Microsomes were then incubated with 30 μM Fe 2+ in an NADPH-generating system, and both production of malondialdehyde (MDA) (a product of lipid peroxidation) and oxidation of αT* were monitored over a time course in the presence and absence of glutathione (GSH). The results indicate virtually complete oxidation of αT* precedes significant membrane lipid peroxidation, and that addition of 5 mM GSH delays both αT* oxidation and subsequent MDA production. This suggests that the previously observed VE-dependent heat labile inhibition of microsomal lipid peroxidation by GSH involves maintaining membrane levels of α-tocopherol

The radioprotective role of Gamma-Tocopherol on cholinergic and electrical activities in the brain of Gamma irradiated rats

International Nuclear Information System (INIS)

M, A.M.; Saada, H.N.

1997-01-01

Data of the present study revealed that whole body gamma exposure of adult male albino rats at 8 Gy causes a significant increase in the acetylcholine (ACh)content of the two cerebral hemispheres concomittant with a marked inhibition in the activity of acetylcholinesterase (AChE) enzyme 1,3,7,and 10 days after irradiation. The electroencephalogram (EEG) activity of frontal cortical area showed a significant increase in the faster frequencies (Bita-rhythm) and a decrease in the slower rhythm (delta - frequencies). Pretreatment of rats with α-tocopherol, 2 hr, prior irradiation provides the rats with a partial protection from the radiation induced changes in the acetent and cholinesterase activity of cerebral hemispheres. Injection of α-tocopherol has also provided the rats with some protection against the changes recorded for EEG activity of the cortical frontal area

Effects of gamma radiation and menadione (vit. K3) on dissolution and dimerization of δ-tocopherol

International Nuclear Information System (INIS)

Kupczyk, B.; Gogolewski, M.

1997-01-01

Effect of ionizing radiation and menadione (vit. K 3 ) on dissolution and dimerization of δ-tocopherol was studied. Mixture of δ-tocopherol and menadione (vit. K 3 ) dissolved in benzene, ethanol or used in substantia were irradiated at 2.5, 5, 10, 20 kGy dose using Co-60 as a radiation source. Dissolution of δ-tocopherol in substantia was lower then disintegration of δ-tocopherol dissolved in benzene or in ethanol. However, we did not observe any significant difference between dissolution of δ-tocopherol in both studied solvents. The number of formed dimers of δ-tocopherol were different for all three cases tested. The quantities of δ-tocopherol dimers were dependent on radiation dose. (author)

Inhibition of glycolysis and growth of colon cancer cells by 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3PO in combination with butyrate, 2-deoxy glucose, 3-bromopyruvate or biguanides

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Lea MA

2015-09-01

Full Text Available Introduction: Glycolysis shows a positive correlation with growth of human colon cancer cells. PFKFB3 is an important enzyme regulating glycolysis in many tumor cells and presents a target for cancer chemotherapy. We studied the action of an inhibitor of PFKFB3, 3-(3-pyridinyl-1-(4-pyridinyl-2-propen-1-one (3PO, as a single agent and in combination with other molecules that affect glycolysis. Materials and methods: Effects on growth were studied in four human colon cancer cell lines. Glucose metabolism was monitored by uptake from the incubation medium and lactic acid production was judged by acidification of the medium. Induction of alkaline phosphatase served as a marker of differentiation. Results: Growth of colon cancer cells was inhibited by 3PO and butyrate but only butyrate induced activation of alkaline phosphatase. Although metformin and phenformin can increase glucose metabolism, they inhibit colon cancer cell growth and can exert additive inhibitory effects in combination with 3PO. Additive growth inhibitory effects with 3PO were also observed with two compounds that inhibit glycolysis: 2-deoxyglucose and 3-bromopyruvate. Conclusion: 3PO was an inhibitor of growth of colon cancer cells and may be a useful agent in combination with other drugs that inhibit colon cancer cell proliferation.

Supplementation of α-Tocopherol Attenuates Minerals Disturbance, Oxidative Stress and Apoptosis Occurring in Favism.

Science.gov (United States)

Koriem, Khaled M M; Arbid, Mahmoud S; Gomaa, Nawal E

2017-10-01

The favism is a metabolic disease that characterized with an acute hemolytic anemia where α-tocopherol is a type of tocopherol accumulated inside the human body. The objective of such a study was established to evaluate the effect of α-tocopherol in favism disorders. A total of 75 human cases were divided into 5 groups as follow; group 1 normal cases without any treatment and group 2 normal cases orally administrated α-tocopherol (200 mg/kg) once a day over 30 days period. Group 3 favism patients without any treatment. Groups 4 and 5 favism patients orally administrated 100 and 200 mg α-tocopherol/kg, respectively once a day over 30 days period. The results obtained revealed that oral administration of α-tocopherol into normal cases over 30 days period did not induce any biological change. In favism, hemoglobin, hematocrit, red and white blood cells, serum glucose, glucose-6-phosphate dehydrogenase, total protein, albumin, globulin, aspartate and alanine aminotransferases, blood glutathione, superoxide dismutase, glutathione peroxidase and serum calcium, phosphorous, sodium, potassium and chloride levels were significantly decreased. On the other hand, serum alkaline phosphatase, bilirubin, selenium, zinc, manganese, copper and iron, malondialdehyde levels showed significant increase in favism. Supplementation with α-tocopherol into favism restores all the above mentioned parameters to approach the normal levels. Also, α-tocopherol has anti-apoptotic effect in favism. In conclusion, α-tocopherol attenuates minerals disturbance, oxidative stress and apoptosis occurring in favism.

Circulating tocopherols and risk of coronary artery disease: A systematic review and meta-analysis.

Science.gov (United States)

Li, Guangxiao; Li, Ying; Chen, Xin; Sun, Hao; Hou, Xiaowen; Shi, Jingpu

2016-05-01

Circulating level of tocopherols was supposed to be associated with risk of coronary artery disease. However, the results from previous studies remain controversial. Therefore, we conducted a meta-analysis based on observational studies to evaluate the association between circulating tocopherols and coronary artery disease risk for the first time. Meta-analysis. PubMed, Embase and Cochrane databases were searched to retrieve articles published during January 1995 and May 2015. Articles were included if they provided sufficient information to calculate the weighted mean difference and its corresponding 95% confidence interval. Circulating level of total tocopherols was significantly lower in coronary artery disease patients than that in controls (weighted mean difference -4.33 μmol/l, 95% confidence interval -6.74 to -1.91, P tocopherol alone was not significantly associated with coronary artery disease risk. Results from subgroup analyses showed that a lower level of circulating total tocopherols was merely associated with higher coronary artery disease risk in studies with higher sex ratio in cases (tocopherols was associated with early onset coronary artery disease rather than late onset coronary artery disease (tocopherols when the studies were stratified by matching status and assay methods. Our findings suggest that a deficiency in circulating total tocopherols might be associated with higher coronary artery disease risk. Whereas circulating α-tocopherol alone could not protect us from developing coronary artery disease. Further prospective studies were warranted to confirm our findings. © The European Society of Cardiology 2015.

Serum carotenoid, retinol and tocopherol concentrations and risk of cervical cancer among Chinese women.

Science.gov (United States)

Zhang, Yuan-Yuan; Lu, Ling; Abliz, Guzalnur; Mijit, Fatima

2015-01-01

Despite many epidemiological studies on the effects of dietary antioxidant micronutrients on risk of cervical cancer, the findings remain uncertain and little evidence is available for serum nutrient markers. The present study aimed to examine the relationship between serum carotenoid, retinol and tocopherol concentrations and risk of cervical cancer among Chinese women. We conducted a hospital-based case- control study in which 358 adults (158 incident cases and 200 controls) were recruited from Xinjiang, China. Serum levels of carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin), retinol, and tocopherols (α-tocopherol and γ-tocopherol) were assessed by reverse-phase high-performance liquid chromatography. We found inverse associations between serum carotenoid (α-carotene, β-carotene, and lutein/zeaxanthin) and tocopherol (α-tocopherol) concentrations and the risk of cervical cancer after adjusting for potential confounders, but a null association for retinol. The ORs for 1-SD increase were 0.71 (95% CI: 0.56- 0.92; p=0.003) for total carotenoids and 0.75 (95% CI: 0.60-0.94; p=0.008) for total tocopherols. These results show that higher serum concentrations of some carotenoids and tocopherols are associated with a lower risk of cervical cancer among Chinese women.

5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT

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Tiong Cheng Sia

2013-08-01

Full Text Available Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit ? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT. In control animals, peristaltic contractions were blocked temporarily by ondansetron (1-10µM and SDZ-205-557 (1-10µM in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis.

High-performance liquid chromatography for determination of α-tocopherol in vegetables

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Marcin Horbowicz

2013-12-01

Full Text Available A simple method for the determination of α-tocopherol in vegetables is described. The procedure consists of the following steps: saponification, extraction, silica-column clean-up, and high-performance liquid chromatography. Elution time for D, L-α-tocopherol was 9.0 min using a Zorbax Sil (250 x 4.6 mm column and an isocratic mobile phase of hexane-methanol (99.3 + 0.7, with a flow rate of 1 ml/min, and detection at 292 nm using a variable UV detector. The average recovery of α-tocopherol was 91.2%, and the minimum detectable amount was 0.1 mg/100 g of fresh vegetable tissue. This method is comparable to gas-chromatographic determination of α-tocopherol, but has fewer analytical steps and gives more reproducible results.

Oxidation in fish oil-enriched mayonnaise 4 : Effect of tocopherol concentration on oxidative deterioration

DEFF Research Database (Denmark)

Jacobsen, Charlotte; Hartvigsen, Karsten; Lund, Pia

2001-01-01

The effect of the water-dispersible tocopherol preparation, Grindox 1032, and the oil-soluble tocopherol preparation, Toco 70, on oxidative stability in fish oil-enriched mayonnaise was examined. The two commercial antioxidant preparations were supplemented in different levels corresponding to 20......-280 ppm tocopherol in addition to the 600 ppm present in the oils used for the mayonnaise. The oxidative stability was assessed by sensory analysis, the tendency of formation of free radicals, and concentrations of lipid hydroperoxides and volatile oxidation products. The effect of tocopherol on oxidation...... depended on the nature and the concentration of the tocopherol preparation employed, and it also depended on the parameters evaluated. Addition of high levels of Grindox 1032 (similar to 140-280 ppm tocopherol) thus decreased the intensity of rancid off-flavor, but increased the formation of fishy off...

Enhanced tocopherol levels during early germination events in Chamaerops humilis var. humilis seeds.

Science.gov (United States)

Siles, Laura; Alegre, Leonor; Tijero, Verónica; Munné-Bosch, Sergi

2015-10-01

Most angiosperms accumulate vitamin E in the form of tocopherols in seeds, exerting a protective antioxidant role. However, several palm trees principally accumulate tocotrienols, rather than tocopherols, in seeds, as it occurs in other monocots. To unravel the protective role of either tocopherols or tocotrienols against lipid peroxidation during seed germination in Chamaerops humilis var. humilis; seed viability, natural and induced germination capacity, seed water content, malondialdehyde levels (as an indicator of the extent of lipid peroxidation) and vitamin E levels (including both tocopherols and tocotrienols) were examined at various germination phases in a simulated, natural seed bank. At the very early stages of germination (operculum removal), malondialdehyde levels increased 2.8-fold, to decrease later up to 74%, thus indicating a transient lipid peroxidation at early stages of germination. Tocopherol levels were absent in quiescent seeds and did not increase during operculum removal, but increased later presumably dampening malondialdehyde accumulation. Thereafter, tocopherols continued increasing, while lipid peroxidation levels decreased. By contrast, tocotrienols levels remained constant or even decreased as germination progressed, showing no correlation with lipid peroxidation levels. We hypothesize that despite their high tocotrienol content, seeds synthesize tocopherols during germination to protect lipids from peroxidation events. Copyright © 2015 Elsevier Ltd. All rights reserved.

Colonic motility and enema spreading

International Nuclear Information System (INIS)

Hardy, J.G.; Wood, E.; Clark, A.G.; Reynolds, J.R.; Queen's Medical Centre, Nottingham

1986-01-01

Radiolabelled enema solution was administered to eight healthy subjects, both in fasted and fed states. Enema spreading was monitored over a 4-h period using gamma scintigraphy and colonic motility was recorded simultaneously using a pressure sensitive radiotelemetry capsule. The rate and extent of enema dispersion were unaffected by eating. Spreading could be correlated with colonic motility and was inhibited by aboral propulsion of the colonic contents. (orig.)

Concomitant consumption of lycopene and fish oil inhibits tumor growth and progression in a mouse xenograft model of colon cancer

Science.gov (United States)

Our previous report showed that concomitant supplementation of lycopene and eicosa-pentaenoic acid synergistically inhibited the proliferation of human colon cancer HT-29 cells in vitro. To validate our findings, the present study investigated whether consumption of lycopene and fish oil would help ...

Modification of radiation-induced sex-linked recessive lethal mutation frequency by tocopherol

International Nuclear Information System (INIS)

Beckman, C.; Roy, R.M.; Sproule, A.

1982-01-01

The present study evaluates the effect of supplementing culture medium with α-tocopherol acetate on the yield of sex-linked recessive lethal mutants induced by X-irradiation in mature sperm of Drosophila. Although tocopherol treatment of males had no impact on the yield of mutations, a drastic reduction in mutation frequency was observed when irradiated males were mated to females raised and subsequently maintained on tocopherol-enriched diet. (orig./MG)

Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition

International Nuclear Information System (INIS)

Hackl, Christina; Stoeltzing, Oliver; Lang, Sven A; Moser, Christian; Mori, Akira; Fichtner-Feigl, Stefan; Hellerbrand, Claus; Dietmeier, Wolfgang; Schlitt, Hans J; Geissler, Edward K

2010-01-01

Activating transcription factor-3 (ATF3) is involved in the complex process of cellular stress response. However, its exact role in cancer is discussed controversially because both tumor suppressive and oncogenic effects have been described. Here we followed-up on our previous observation that inhibition of Hsp90 may increase ATF3 expression and sought to determine the role of ATF3 in colon cancer. Regulation of ATF3 was determined in cancer cells using signaling inhibitors and a heat-shock protein-90 (Hsp90) antagonist. Human HCT116 cancer cells were stably transfected with an ATF3-shRNA or a luciferase-shRNA expression plasmid and alterations in cell motility were assessed in migration assays. The impact of ATF3 down-regulation on cancer growth and metastasis were investigated in a subcutaneous tumor model, a model of hepatic tumor growth and in a model of peritoneal carcinomatosis. Human colon cancer tissues were analyzed for ATF3 expression. The results show that therapeutic Hsp90 inhibition substantially up-regulates the expression of ATF3 in various cancer cells, including colon, gastric and pancreatic cancer. This effect was evident both in vitro and in vivo. RNAi mediated knock-down of ATF3 in HCT116 colon cancer cells significantly increased cancer cell migration in vitro. Moreover, in xenogenic mouse models, ATF3 knock-down promoted subcutaneous tumor growth and hepatic metastasis, as well as peritoneal carcinomatosis. Importantly, ATF3 expression was lower in human colon cancer specimens, as compared to corresponding normal surrounding tissues, suggesting that ATF3 may represent a down-regulated tumor suppressor in colon cancer. In conclusion, ATF3 down-regulation in colon cancer promotes tumor growth and metastasis. Considering that blocking Hsp90 induces ATF3 expression, Hsp90 inhibition may represent a valid strategy to treat metastatic colon cancer by up-regulating this anti-metastatic transcription factor

Targeting S100P Inhibits Colon Cancer Growth and Metastasis by Lentivirus-Mediated RNA Interference and Proteomic Analysis

Science.gov (United States)

Jiang, Lei; Lai, Yiu-Kay; Zhang, Jinfang; Wang, Hua; Lin, Marie CM; He, Ming-liang; Kung, Hsiang-fu

2011-01-01

S100P was recently found to be overexpressed in a variety of cancers and is considered a potential target for cancer therapy, but the functional role or mechanism of action of S100P in colon cancer is not fully understood. In the present study, we knocked down the gene expression of S100P in colon cancer cells using lentivirus-mediated RNA interference. This step resulted in significant inhibition of cancer cell growth, migration and invasion in vitro and tumor growth and liver metastasis in vivo. Moreover, S100P downstream target proteins were identified by proteomic analysis in colon cancer DLD-1 cells with deletion of S100P. Knockdown of S100P led to downregulation of thioredoxin 1 and β-tubulin and upregulation of Rho guanosine diphosphate (GDP) dissociation inhibitor α (RhoGDIA), all potential therapeutic targets in cancer. Taken together, these findings suggest that S100P plays an important role in colon tumorigenesis and metastasis, and the comprehensive and comparative analyses of proteins associated with S100P could contribute to understanding the downstream signal cascade of S100P, leading to tumorigenesis and metastasis. PMID:21327297

α-Tocopherol modulates the low density lipoprotein receptor of human HepG2 cells

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Bottema Cynthia DK

2003-05-01

Full Text Available Abstract The aim of this study was to determine the effects of vitamin E (α-tocopherol on the low density lipoprotein (LDL receptor, a cell surface protein which plays an important role in controlling blood cholesterol. Human HepG2 hepatoma cells were incubated for 24 hours with increasing amounts of α, δ, or γ-tocopherol. The LDL receptor binding activity, protein and mRNA, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase mRNA, cell cholesterol and cell lathosterol were measured. The effect of α-tocopherol was biphasic. Up to a concentration of 50 μM, α-tocopherol progressively increased LDL receptor binding activity, protein and mRNA to maximum levels 2, 4 and 6-fold higher than control, respectively. The HMG-CoA reductase mRNA and the cell lathosterol concentration, indices of cholesterol synthesis, were also increased by 40% over control by treatment with 50 μM α-tocopherol. The cell cholesterol concentration was decreased by 20% compared to control at 50 μM α-tocopherol. However, at α-tocopherol concentrations higher than 50 μM, the LDL receptor binding activity, protein and mRNA, the HMG-CoA reductase mRNA and the cell lathosterol and cholesterol concentrations all returned to control levels. The biphasic effect on the LDL receptor was specific for α-tocopherol in that δ and γ-tocopherol suppressed LDL receptor binding activity, protein and mRNA at all concentrations tested despite the cells incorporating similar amounts of the three homologues. In conclusion, α-tocopherol, exhibits a specific, concentration-dependent and biphasic "up then down" effect on the LDL receptor of HepG2 cells which appears to be at the level of gene transcription. Cholesterol synthesis appears to be similarly affected and the cell cholesterol concentration may mediate these effects.

Synthesis and Theoretical Study of Molecularly Imprinted Nanospheres for Recognition of Tocopherols

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Chartchalerm Isarankura-Na-Ayudhya

2009-08-01

Full Text Available Molecular imprinting is a technology that facilitates the production of artificial receptors toward compounds of interest. The molecularly imprinted polymers act as artificial antibodies, artificial receptors, or artificial enzymes with the added benefit over their biological counterparts of being highly durable. In this study, we prepared molecularly imprinted polymers for the purpose of binding specifically to tocopherol (vitamin E and its derivative, tocopherol acetate. Binding of the imprinted polymers to the template was found to be two times greater than that of the control, non-imprinted polymers, when using only 10 mg of polymers. Optimization of the rebinding solvent indicated that ethanol-water at a molar ratio of 6:4 (v/v was the best solvent system as it enhanced the rebinding performance of the imprinted polymers toward both tocopherol and tocopherol acetate with a binding capacity of approximately 2 mg/g of polymer. Furthermore, imprinted nanospheres against tocopherol was successfully prepared by precipitation polymerization with ethanol-water at a molar ratio of 8:2 (v/v as the optimal rebinding solvent. Computer simulation was also performed to provide mechanistic insights on the binding mode of template-monomer complexes. Such polymers show high potential for industrial and medical applications, particularly for selective separation of tocopherol and derivatives.

Quantitative determination of alpha-tocopherol in Arbutus unedo by TLC-densitometry and colorimetry.

Science.gov (United States)

Kivçak, B; Mert, T

2001-08-01

A quantitative determination of alpha-tocopherol in Arbutus unedo leaves was established by TLC-densitometry and colorimetry. Data obtained by TLC-densitometry were compared with those obtained by colorimetry. Also, the alpha-tocopherol content in leaves collected at different times of the year was studied comparatively. The highest amount of alpha-tocopherol was found in the March collection.

Luteolin inhibits the colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition: an experimental study

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Xin Meng

2017-11-01

Full Text Available Objective: To study the regulating effect of luteolin on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition. Methods: Colon cancer HT-29 cells were cultured and randomly divided into two groups, control group were treated with serum-free medium without drugs and LUT group were treated with serum-free medium containing luteolin. After 24 h of treatment, cells were collected to extract RNA, and then fluorescent quantitative PCR method was used to determine the mRNA expression of proliferation genes, migration genes and epithelial-mesenchymal transition genes. Results: After 24 h of luteolin treatment, Lrig1, TSPYL5, Bim, SOX15 and DLC1 mRNA expression in LUT group were significantly higher than those in control group while RPS15a, Bad, TRPV5, TRPV6, PLD2, IBP, SphK1, FAK, Vimentin and N-cadherin mRNA expression were significantly lower than those in control group. Conclusion: Luteolin has inhibiting effect on colon cancer HT-29 cell proliferation, migration and epithelial-mesenchymal transition.

α-Tocopherol-5-Me-T. Synthesis, purification and characterization

International Nuclear Information System (INIS)

Corol-Cucu, Delia-Irina; Chiper, Diana; Mihaila, V.; Negoita, N.

2000-01-01

The E vitamine is named 'vitamine of antisterility' because it is essential for good functioning of genital organs. It is involved in cellular oxidation processes, in muscle creatinine metabolism and metabolism of saccharides encouraging glycogen deposition in tissues. The name of E vitamine is given to eight different compounds which have a ring with methyl and hydroxyl groups. Four of them, named tocopherols, contain a lateral saturated chain which derives from fitol and the others, named tocotrienols, have three double bonds in the lateral chain.This paper refers to synthesis, purification and characterization of α-tocopherol labelled with tritium in 5-methyl position. Tritium is different by the other hydrogen isotopes because it is the only radioactive isotope of hydrogen. The α-tocopherol-5-Me-T. The dry HCl is bubbled in a mixture of γ-tocopherol, paraformaldehyde and ZnCl 2 powder in dry Et 2 O. This solution remains at a standstill for a few hours and after that water is slowly added under stirring at low temperature ( 2 SO 4 . The next step is filtration and evaporation of ether stratum under nitrogen environment. One obtains 5-Cl-Me-α-tocopherol. For synthesis of α-tocopherol-5-Me-T the replacement of chlorine with tritium is done through catalytic dechlorination with Pd/C or Pd/CaCO 3 (10% Pd) as catalysts. One half of 5-Me-Cl compound is solved in dioxane and then the catalyst and deuterium are added under stirring, for 2 hours at room temperature. After filtration and washing with MeOH, the solvent is eliminated under vacuum conditions. Thus one obtains α-tocopherol-5-Me-T. The purification has been carried out through thin layer chromatography with C 6 H 6 as solvent (Al 2 O 3 as support) or solvent system C 6 H 6 : CH 3 OH (98:2, v/v) (silicagel as support). The determination of activity is carried out with LSC (Liquid Scintillation Counter). A 98% purity was determined through TLC in the same conditions while determination of activity

Vasohibin-1 suppresses colon cancer

OpenAIRE

Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

2015-01-01

Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and co...

Derricin and derricidin inhibit Wnt/β-catenin signaling and suppress colon cancer cell growth in vitro.

Directory of Open Access Journals (Sweden)

Barbara F Fonseca

Full Text Available Overactivation of the Wnt/β-catenin pathway in adult tissues has been implicated in many diseases, such as colorectal cancer. Finding chemical substances that can prevent this phenomenon is an emerging problem. Recently, several natural compounds have been described as Wnt/β-catenin inhibitors and might be promising agents for the control of carcinogenesis. Here, we describe two natural substances, derricin and derricidin, belonging to the chalcone subclass, that show potent transcriptional inhibition of the Wnt/β-catenin pathway. Both chalcones are able to affect the cell distribution of β-catenin, and inhibit Wnt-specific reporter activity in HCT116 cells and in Xenopus embryos. Derricin and derricidin also strongly inhibited canonical Wnt activity in vitro, and rescued the Wnt-induced double axis phenotype in Xenopus embryos. As a consequence of Wnt/β-catenin inhibition, derricin and derricidin treatments reduce cell viability and lead to cell cycle arrest in colorectal cancer cell lines. Taken together, our results strongly support these chalcones as novel negative modulators of the Wnt/β-catenin pathway and colon cancer cell growth in vitro.

Antioxidant effect of mono- and dihydroxyphenols in sunflower oil with different levels of naturally present tocopherols

Science.gov (United States)

Hrádková, Iveta; Merkl, Roman; Šmidrkal, Jan; Kyselka, Jan; Filip, Vladimír

2013-01-01

Antioxidant properties of mono- and dihydroxyphenolic acids and their alkyl esters were examined, with emphasis on the relationship between their molecular structure and antioxidant activity. Test media with different tocopherol level were used for determining the oxidative stability: original refined sunflower oil (total tocopherols 149.0 mg/kg), partially tocopherol-stripped sunflower oil (total tocopherols 8.7 mg/kg) and distilled fatty acid methyl esters (FAME) as a tocopherol-free medium. The chemical reaction of tocopherols with diazomethane tested for the purpose to eliminate their antioxidant activity failed due to the negligible degree of methylation of hydroxyl group in the tocopherol molecule. Caffeic acid and protocatechuic acid (3,4-dihydroxyphenolic acids) and their alkyl esters were found to be more active antioxidants than monohydroxyphenolic acid (p-hydroxybenzoic acid), 2,5-dihydroxyphenolic acid (gentisic acid), 3-methoxy-4-hydroxyphenolic acids (vanillic and ferulic acids) and their corresponding alkyl esters. Naturally present tocopherols in refined sunflower oil proved to have a synergistic effect on gentisic acid but not on its alkyl esters. In contrast, tocopherols showed an antagonistic effect on alkyl esters of caffeic acid, because their protection factors decreased with increasing level of tocopherols in the test medium. Moreover, the antioxidant activity of these alkyl esters decreased with increasing length of their alkyl chain in conformity with the polar paradox hypothesis. Practical applications: Tocopherols as naturally present antioxidants influence considerably the antioxidant activity of other antioxidants added to plant oils used as a test medium. Distilled fatty acid methyl esters prepared from refined sunflower oil may serve as an optimal tocopherol-free test medium. Some alkyl esters of phenolic acids were evaluated to be applicable as natural more lipophilic antioxidants in comparison with phenolic acids. PMID:23997655

Correlation of repressed transcription of alpha-tocopherol transfer protein with serum alpha-tocopherol during hepatocarcinogenesis

NARCIS (Netherlands)

Wu, C. G.; Hoek, F. J.; Groenink, M.; Reitsma, P. H.; van Deventer, S. J.; Chamuleau, R. A.

1997-01-01

Using a subtraction-enhanced display technique, we identified a rodent alpha-tocopherol transfer protein (alpha-TTP) cDNA which exhibited markedly lower messenger RNA (mRNA) amounts in rat hepatocellular carcinoma (HCC) than in healthy controls. Several lines of evidence have substantiated that

Roselle (Hibiscus sabdariffa) seed oil is a rich source of gamma-tocopherol.

Science.gov (United States)

Mohamed, R; Fernández, J; Pineda, M; Aguilar, M

2007-04-01

The antioxidant potential of roselle (Hibiscus sabdariffa L.) extracts was studied. Different plant organs, including seeds, stems, leaves, and sepals, were analyzed with respect to their water-soluble antioxidant capacity, lipid-soluble antioxidant capacity, and tocopherol content, revealing that roselle seeds are a good source of lipid-soluble antioxidants, particularly gamma-tocopherol. Roselle seed oil was extracted and characterized, and its physicochemical parameters are summarized: acidity, 2.24%; peroxide index, 8.63 meq/kg; extinction coefficients at 232 (k(232)) and 270 nm (k(270)), 3.19 and 1.46, respectively; oxidative stability, 15.53 h; refractive index, 1.477; density, 0.92 kg/L; and viscosity, 15.9 cP. Roselle seed oil belongs to the linoleic/oleic category, its most abundant fatty acids being C18:2 (40.1%), C18:1 (28%), C16:0 (20%), C18:0 (5.3%), and C19:1 (1.7%). Sterols include beta-sitosterol (71.9%), campesterol (13.6%), Delta-5-avenasterol (5.9%), cholesterol (1.35%), and clerosterol (0.6%). Total tocopherols were detected at an average concentration of 2000 mg/kg, including alpha-tocopherol (25%), gamma-tocopherol (74.5%), and delta-tocopherol (0.5%). The global characteristics of roselle seed oil suggest that it could have important industrial applications, adding to the traditional use of roselle sepals in the elaboration of karkade tea.

A correlation between tocopherol content and antioxidant activity in seeds and germinating seeds of soybean cultivars.

Science.gov (United States)

Lee, Yu Young; Park, Hyang Mi; Hwang, Tae Young; Kim, Sun Lim; Kim, Mi Jung; Lee, Seuk Ki; Seo, Min Jung; Kim, Kee Jong; Kwon, Young-Up; Lee, Sang Chul; Kim, Yul Ho

2015-03-15

Tocopherols are crucial lipid-soluble antioxidants and essential nutrients. There is increasing interest in the biofortification of crops with vitamin E for reducing micronutrient malnutrition. However, relatively little is known about the development of soybean cultivars with high levels of tocopherol through combined breeding. Tocopherol contents of seeds and germinating seeds of 28 Korean soybean cultivars were analyzed and evaluated for health-promoting activities. Total tocopherol concentrations ranged from 203.9 to 503.1 µg g⁻¹ in seeds and from 20.1 to 230.1 µg g⁻¹ in germinating seeds. The traditional landraces of HaNagari (HN, 503.1 µg g⁻¹), Orialtae (OL, 486.6 µg g⁻¹), SuMoktae (SM, 476.5 µg g⁻¹) and SoRitae (SR, 475.5 µg g⁻¹) showed high levels of tocopherol content. The contents of the four isomers of tocopherol in seeds and germinating seeds were correlated with lipid peroxidation. The γ- and δ-tocopherol contents in seeds were related to 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity (0.434; P tocopherol content was higher in soybean landraces as compared with modern cultivars developed by cross-breeding. These results suggest that soybean breeding is necessary to increase tocopherol levels. © 2014 Society of Chemical Industry.

Effects of octreotide and a-tocopherol on bacterial translocation in experimental intestinal obstruction: a microbiological, light and electronmicroscopical study.

Science.gov (United States)

Reis, E; Kama, N A; Coskun, T; Korkusuz, P; Ors, U; Aksoy, M; Kulaçoglu, S

1997-01-01

Bacterial translocation induced by intestinal obstruction is suggested to be due to increased intestinal luminal volume, leading to intestinal overgrowth with certain enteric microorganisms and intestinal mucosal damage. If this suggestion is true, maintenance of intestinal mucosal integrity by a cytoprotective agent, a-tocopherol, and inhibition of gastrointestinal secretions by octreotide should decrease the incidence of bacterial translocation and extent of mucosal injury due to intestinal obstruction. Complete intestinal obstruction was created in the distal ileum of male Wistar Albino rats by a single 3-0 silk suture. The animals received subcutaneous injections of 1 ml of physiologic saline (group 1) (PS 24) and 1 ml of saline containing octreotide acetate (100 micrograms/kg) (group 2) (OC 24), at 0, 12 and 24 hours of obstruction. In group 3 (PS 48) and group 4 (OC 48), the rats were treated with subcutaneous physiologic saline (1 ml) and octreotide acetate (100 micrograms/kg), respectively, beginning at the time of obstruction and every 12 hours for 48 hours. The rats in group 5 (Toc 24), were pretreated with intramuscular a-tocopherol 500 mg/kg on day 1 and 8, and underwent laparotomy on day 9. A third dose of a-tocopherol was injected at the time of obstruction on day 9 and no treatment was given thereafter. We tested the incidence of bacterial translocation in systemic organs and circulation and evaluated the histopathological changes in all groups. Treatment with octreotide acetate was found to be ineffective in reducing the incidence of translocation, with no histopathological improvement. Mucosal damage scores, on the other hand, in the a-tocopherol group were statistically less than those in the octreotide and control groups (p < 0.05). Additionally, a-tocopherol treatment decreased the incidence of organ invasion with translocating bacteria, although this difference did not reach statistical significance. Octreotide acetate treatment in complete

1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial–mesenchymal transition in colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Shanwen; Zhu, Jing; Zuo, Shuai; Ma, Ju; Zhang, Junling; Chen, Guowei; Wang, Xin; Pan, Yisheng; Liu, Yucun; Wang, Pengyuan, E-mail: wangpengyuan2014@126.com

2015-12-04

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial–mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells. - Highlights: • TGF-β1/β2-induced model of EMT was used in this study to test the effect of 1,25(OH)2D3 on EMT in colon cancer cells. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased migration and invasion. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased level of EMT-related transcription factors. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased expression of F-actin in SW-480 cells.

Colon in acute intestinal infection.

Science.gov (United States)

Guarino, Alfredo; Buccigrossi, Vittoria; Armellino, Carla

2009-04-01

The colon is actively implicated in intestinal infections not only as a target of enteric pathogens and their products but also as a target organ for treatment. In the presence of diarrhea, both of osmotic and secretory nature, the colon reacts with homeostatic mechanisms to increase ion absorption. These mechanisms can be effectively exploited to decrease fluid discharge. A model of intestinal infections using rotavirus (RV) in colonic cells was set up and used to define a dual model of secretory and osmotic diarrhea in sequence. Using this model, antidiarrheal drugs were tested, namely zinc and the enkephalinase inhibitor racecadotril. Zinc was able to decrease the enterotoxic activity responsible for secretory diarrhea. It also inhibited the cytotoxic effect of RV. The mechanism of zinc was related at least in part to the activation of MAPK activity, but also a direct antiviral effect was observed. Racecadotril showed a potent and selective inhibition of active secretion, being particularly effective in the first phase of RV diarrhea. The use of drugs active at the colonic level, therefore, offers effective options to treat intestinal infections in childhood. In addition, the colon is the natural site of colonic microflora, a target of probiotic therapy, which is the first line of approach recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition to treat infectious diarrhea.

Biosynthesis, structural, and functional attributes of tocopherols in planta; past, present, and future perspectives.

Science.gov (United States)

Hussain, Nazim; Irshad, Faiza; Jabeen, Zahra; Shamsi, Imran Haider; Li, Zhilan; Jiang, Lixi

2013-07-03

Tocopherols are lipophilic molecules, ubiquitously synthesized in all photosynthetic organisms. Being a group of vitamin E compounds, they play an essential role in human nutrition and health. Despite their structural and functional attributes as important antioxidants in plants, it would be misleading to ignore the potential roles of tocopherols beyond their antioxidant properties in planta. Detailed characterization of mutants and transgenic plants, including Arabidopsis (vte1, vte2, vte4, and so on), maize (sxd1) mutants, and transgenic potato and tobacco lines altered in tocopherol biosynthesis and contents, has led to surprising outcomes regarding the additional functions of these molecules. Thus, the aim of this review is to highlight the past and present research findings on tocopherols' structural, biosynthesis, and functional properties in plants. Special emphasis is given to their suggested functions in planta, such as cell signaling, hormonal interactions, and coordinated response of tocopherols to other antioxidants under abiotic stresses. Moreover, some important questions about possible new functions of tocopherols will be discussed as future prospects to stimulate further research.

In vivo regulation of gene transcription by alpha- and gamma-Tocopherol in murine T lymphocytes

Science.gov (United States)

Of the 8 different analogues (alpha-, beta-, gamma-, delta-tocopherols and tocotrienols) designated as vitamin E, alpha-tocopherol (a-T) has been mostly studied, together with gamma-tocopherol (g-T) which is abundant in the US diet. We compared the effect of dietary supplementation with adequate or ...

Effects of nano-emulsion preparations of tocopherols and tocotrienols on oxidative stress and osteoblast differentiation

Directory of Open Access Journals (Sweden)

Song Liang-Song

2017-01-01

Full Text Available Tocopherols and tocotrienols are two groups of compounds in the vitamin E family, of which the tocopherols are widely used as antioxidant dietary supplements. Recent studies have shown mixed observations for tocopherol functions in bone homeostasis. We have evaluated the potency of suspension- and nano-emulsion formulation-based delivery of different vitamin E family members in lipopolysaccharide (LPS-induced oxidative stress and osteoblast differentiation. Our results showed the both tocopherols and tocotrienols could reduce oxidative stress as evaluated by the levels of reactive oxygen species (ROS. Their effects were enhanced when applied in the nano-emulsion mode of delivery due to increased bioavailability. In addition, our results showed that tocotrienols increased osteoblast differentiation, while tocopherols showed reduced osteoblast differentiation, which may be due to their differential effects on SMAD and p65 signaling. Together, these findings indicate that tocotrienols delivered through nano-emulsion exhibit superior antioxidant properties and osteoblast differentiation, and could serve as a better alternative to tocopherol-based vitamin E supplements.

Chlorophyll Degradation: The Tocopherol Biosynthesis-Related Phytol Hydrolase in Arabidopsis Seeds Is Still Missing1[C][W][OPEN

Science.gov (United States)

Zhang, Wei; Liu, Tianqi; Ren, Guodong; Hörtensteiner, Stefan; Zhou, Yongming; Cahoon, Edgar B.; Zhang, Chunyu

2014-01-01

Phytyl diphosphate (PDP) is the prenyl precursor for tocopherol biosynthesis. Based on recent genetic evidence, PDP is supplied to the tocopherol biosynthetic pathway primarily by chlorophyll degradation and sequential phytol phosphorylation. Three enzymes of Arabidopsis (Arabidopsis thaliana) are known to be capable of removing the phytol chain from chlorophyll in vitro: chlorophyllase1 (CLH1), CLH2, and pheophytin pheophorbide hydrolase (PPH), which specifically hydrolyzes pheophytin. While PPH, but not chlorophyllases, is required for in vivo chlorophyll breakdown during Arabidopsis leaf senescence, little is known about the involvement of these phytol-releasing enzymes in tocopherol biosynthesis. To explore the origin of PDP for tocopherol synthesis, seed tocopherol concentrations were determined in Arabidopsis lines engineered for seed-specific overexpression of PPH and in single and multiple mutants in the three genes encoding known dephytylating enzymes. Except for modestly increasing tocopherol content observed in the PPH overexpressor, none of the remaining lines exhibited significantly reduced tocopherol concentrations, suggesting that the known chlorophyll-derived phytol-releasing enzymes do not play major roles in tocopherol biosynthesis. Tocopherol content of seeds from double mutants in NONYELLOWING1 (NYE1) and NYE2, regulators of chlorophyll degradation, had modest reduction compared with wild-type seeds, although mature seeds of the double mutant retained significantly higher chlorophyll levels. These findings suggest that NYEs may play limited roles in regulating an unknown tocopherol biosynthesis-related phytol hydrolase. Meanwhile, seeds of wild-type over-expressing NYE1 had lower tocopherol levels, suggesting that phytol derived from NYE1-dependent chlorophyll degradation probably doesn’t enter tocopherol biosynthesis. Potential routes of chlorophyll degradation are discussed in relation to tocopherol biosynthesis. PMID:25059706

L-rhamnose as a source of colonic propionate inhibits insulin secretion but does not influence measures of appetite or food intake.

Science.gov (United States)

Darzi, Julia; Frost, Gary S; Swann, Jonathan R; Costabile, Adele; Robertson, M Denise

2016-03-01

Activation of free fatty acid receptor (FFAR)2 and FFAR3 via colonic short-chain fatty acids, particularly propionate, are postulated to explain observed inverse associations between dietary fiber intake and body weight. Propionate is reported as the predominant colonic fermentation product from l-rhamnose, a natural monosaccharide that resists digestion and absorption reaching the colon intact, while effects of long-chain inulin on appetite have not been extensively investigated. In this single-blind randomized crossover study, healthy unrestrained eaters (n = 13) ingested 25.5 g/d l-rhamnose, 22.4 g/d inulin or no supplement (control) alongside a standardized breakfast and lunch, following a 6-d run-in to investigate if appetite was inhibited. Postprandial qualitative appetite, breath hydrogen, and plasma glucose, insulin, triglycerides and non-esterified fatty acids were assessed for 420 min, then an ad libitum meal was provided. Significant treatment x time effects were found for postprandial insulin (P = 0.009) and non-esterified fatty acids (P = 0.046) with a significantly lower insulin response for l-rhamnose (P = 0.023) than control. No differences between treatments were found for quantitative and qualitative appetite measures, although significant treatment x time effects for meal desire (P = 0.008) and desire to eat sweet (P = 0.036) were found. Breath hydrogen was significantly higher with inulin (P = 0.001) and l-rhamnose (P = 0.009) than control, indicating colonic fermentation. These findings suggest l-rhamnose may inhibit postprandial insulin secretion, however neither l-rhamnose or inulin influenced appetite. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alpha-Tocopherol Counteracts the Cytotoxicity Induced by Ochratoxin A in Primary Porcine Fibroblasts

DEFF Research Database (Denmark)

Fusi, Elenora; Rebucci, Raffaella; Pecorini, Chiara

2010-01-01

The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in counteracting its toxicity....... Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM α-tocopherol significantly (P tocopherol...

Determination of α-tocopherol by reversed-phase HPLC in feed and animal-derived foods without saponification.

Science.gov (United States)

Claeys, Erik; Vossen, Els; De Smet, Stefaan

2016-01-30

The analysis of α-tocopherol in feed and animal-derived foods usually involves a saponification step. However, since saponification often leads to losses of α-tocopherol, a method for the determination of α-tocopherol in feed and in animal-derived foods was developed without a saponification step. In this method, α-tocopherol is extracted with hot ethanol and the co-extracted fat is removed by centrifugation. Removal of the fat fraction is made possible by the addition of water, to achieve an ethanol:water ratio of 40:7, followed by cooling on ice before centrifugation. This procedure allows removal of the fat fraction, while α-tocopherol is retained. Matrices differing in gross composition and α-tocopherol content were analyzed: fresh pork, cooked ham, subcutaneous fat, liver, egg yolk, milk and a compound pig feed. Higher α-tocopherol concentrations were found for this novel method compared to a conventional method with saponification, particularly for subcutaneous fat (P saponification method (66-90%; for subcutaneous fat saponification results in higher extraction yields and recoveries compared to the saponification method. © 2015 Society of Chemical Industry.

HIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-glycoprotein.

Directory of Open Access Journals (Sweden)

Jianfang Chen

Full Text Available Multidrug resistance (MDR is one of the major reasons chemotherapy-based treatments fail. Hypoxia is generally associated with tumor chemoresistance. However, the correlation between the heterodimeric hypoxia-inducible factor-1 (HIF-1 and the multidrug resistance (MDR1 gene/transporter P-glycoprotein (P-gp remains unclear. This study aims to explore the molecular mechanisms of reversing colon cancer MDR by focusing on the target gene HIF-1α.A chemotherapeutic sensitivity assay was used to observe the efficiency of MDR reversal in LoVo multicellular spheroids (MCS. The apoptotic level induced by different drugs was examined by flow cytometry (FCM. Binding of HIF-1α to the MDR1 gene promoter was evaluated by Chromatin immunoprecipitation (ChIP. The relationship between HIF-1α/P-gp expression and sensitivity to chemotherapy was analyzed.The sensitivity of LoVo MCS to all four chemotherapy drugs was decreased to varying degrees under hypoxic conditions. After silencing the HIF-1α gene, the sensitivities of LoVo MCS to all four chemotherapy drugs were restored. The apoptotic levels that all the drugs induced were all decreased to various extents in the hypoxic group. After silencing HIF-1α, the apoptosis level induced by all four chemotherapy drugs increased. The expression of HIF-1α and P-gp was significantly enhanced in LoVo MCS after treatment with hypoxia. Inhibiting HIF-1α significantly decreased the expression of MDR1/P-gp mRNA or protein in both the LoVo monolayers and LoVo MCS. The ChIP assay showed that HIF-1α was bound to the MDR1 gene promoter. Advanced colon carcinoma patients with expression of both HIF-1α and P-gp were more resistant to chemotherapy than that with non expression.HIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-gp. The expression of HIF-1α and MDR1/P-gp can be used as a predictive marker for chemotherapy resistance in colon cancer.

Up-regulation of CNDP2 facilitates the proliferation of colon cancer.

Science.gov (United States)

Xue, Conglong; Zhang, Zhenwei; Yu, Honglan; Yu, Miao; Yuan, Kaitao; Yang, Ting; Miao, Mingyong; Shi, Hanping

2014-05-21

Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.

/SIGMA PHI/-tocopherol: modifier of the phase state of the lipid bilayer

International Nuclear Information System (INIS)

Skrypin, V.I.; Bratkcovskaya, L.B.; Erin, A.N.; Kagan, V.E.

1985-01-01

This paper determines the action of low (near-physiological) concentrations of alpha-tocopherol on the character of the gel-liquid crystal transition in a lipid bilayer containing free fatty acids. Fifty mM of K + -phosphate buffer was made up in D 2 O and kept for several hours to enable substitution of H 1 by D 2, after which the buffer was dried and redissolved in D 2 O. The graphs of temperature dependence of relative signal intensity of protons of methylene groups in liposomes of different composition are presented. It is shown that the stabilizing action of alpha-tocopherol on the phase state of the lipid bilayer of membranes is one of the mechanisms by which the recently demonstrated ability of alpha-tocopherol to protect biological membranes against the injurious action of free fatty acids, through the formation of complexes of alpha-tocopherol with fatty acides, may be effected

Protective effect of exercise and alpha tocopherol on atherosclerosis promotion in hypercholesterolemic domestic rabbits

Science.gov (United States)

Shekh, Mudhir S.; Mahmud, Almas M. R.

2017-09-01

This study was designed to determine effects of exercise training (Moderate and severe) and alpha tocopherol on lipid profiles and organ weights in hypercholesterolemic domestic rabbits. Hypercholesterolemia (HC) and atherosclerotic lesions were induced by feeding the male rabbits the standard chow supplemented with 1% cholesterol (atherogenic diet) for 36 days. Experimental rabbits were divided into seven groups: normal (T1), HC control (T2), HC plus alpha tocopherol (0.5mg /animal/day) (T3), HC plus moderate exercise 40 minutes/day (0.5km/day) 5 days/week (T4), HC plus severe exercise 40 minutes/day (1km/day) 5 days/week (T5), HC plus alpha tocopherol plus moderate exercise (T6) and HC plus alpha tocopherol plus severe exercise (T7). After the treatment period of 36th day, blood samples were collected and total cholesterol (TC), Triglyceride (TG), Very low-density lipoprotein (VLDL)-cholesterol, High-density lipoproteins (HDL)-cholesterol, Low-density lipoprotein (LDL)-cholesterol, serum glucose, body and organ weights were assayed and compared with hypercholesterolemic control. Combination of moderate exercise with alpha tocopherol produced significant reduction (Pgroup showed no significant change in all lipid profiles. However, the decrement in the above parameters was comparable with hypercholesterolemic rabbits in combination of severe exercise with alpha tocopherol. The results suggest that the combination of moderate exercise with alpha tocopherol can be exploited for prevention of atherosclerosis in hypercholesterolemic rabbits.

Demonstration of specific binding sites for 3H-RRR-alpha-tocopherol on human erythrocytes

International Nuclear Information System (INIS)

Kitabchi, A.E.; Wimalasena, J.

1982-01-01

Previous work from our laboratory demonstrated specific binding sites for 3 H-RRR-alpha-tocopherol ( 3 H-d alpha T) in membranes of rat adrenal cells. As tocopherol deficiency is associated with increased susceptibility of red blood cells to hemolysis, we investigated tocopherol binding sites in human RBCs. Erythrocytes were found to have specific binding sites for 3 H-d alpha T that exhibited saturability and time and cell-concentration dependence as well as reversibility of binding. Kinetic studies of binding demonstrated two binding sites--one with high affinity (Ka of 2.6 x 10(7) M-1), low capacity (7,600 sites per cell) and the other with low affinity (1.2 x 10(6) M-1), high capacity (150,000 sites per cell). In order to localize the binding sites further, RBCs were fractionated and greater than 90% of the tocopherol binding was located in the membranes. Similar to the findings in intact RBCs, the membranes exhibited two binding sites with a respective Ka of 3.3 x 10(7) M-1 and 1.5 x 10(6) M-1. Specificity data for binding demonstrated 10% binding for RRR-gamma-tocopherol, but not other tocopherol analog exhibited competition for 3 H-d alpha T binding sites. Instability data suggested a protein nature for these binding sites. Preliminary studies on Triton X-100 solubilized fractions resolved the binding sites to a major component with an Mr of 65,000 and a minor component with an Mr of 125,000. We conclude that human erythrocyte membranes contain specific binding sites for RRR-alpha-tocopherol. These sites may be of physiologic significance in the function of tocopherol on the red blood cell membrane

Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Science.gov (United States)

Albanes, Demetrius; Till, Cathee; Klein, Eric A; Goodman, Phyllis J; Mondul, Alison M; Weinstein, Stephanie J; Taylor, Philip R; Parnes, Howard L; Gaziano, J Michael; Song, Xiaoling; Fleshner, Neil E; Brown, Powel H; Meyskens, Frank L; Thompson, Ian M

2014-09-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We, therefore, examined whether presupplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0-7.9 years). Incidence of prostate cancer as a function of plasma α-tocopherol, γ-tocopherol, and supplementation with α-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma γ-tocopherol was not associated with prostate cancer. Men with higher α-tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88-1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44-1.62; P-trend = 0.66]. We found a strong positive plasma α-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29-3.22; P-trend = 0.005]. A positive plasma α-tocopherol-prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7-10; overall Q5 HR, 1.59; 95% CI, 1.13-2.24; P-trend = 0.001; among men receiving selenomethionine, Q5 HR, 2.12; 95% CI, 1.32-3.40; P-trend = 0.0002). Our findings indicate that higher plasma α-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biologic interaction between α-tocopherol and selenium itself or selenomethionine. ©2014 American Association for Cancer Research.

Two approaches in preparation for cogeneration alpha-tocopherol and biodiesel from cottonseed

Energy Technology Data Exchange (ETDEWEB)

Zhu, Q.-L.; Zang, L.-Y.; Zhang, L.; Yun, Z. [Nanjing University of Technology (China)

2012-02-15

Vitamin E is a group of lipid soluble antioxidants that is widely used in the food, cosmetic and medical industries. It is comprised of four tocopherols and four tocotrienols, i.e. alpha, beta, gamma and delta, which are characterized by a chromanol ring structure with a distinct substitution pattern of methyl groups. This paper presents two approaches in preparation for co-generation of alpha-tocopherol and biodiesel from cottonseed. The approaches are a two-step process and a direct alkaline trans-esterification process. Using single factor experiments and an orthogonal design method, the effects of certain factors on the alpha-tocopherol recovery and conversion of cottonseed oil to biodiesel in both processes was systematically studied. In the two-step process, biodiesel and alpha-tocopherol were produced using a two-phase solvent combined with base-catalyzed trans-esterification. It was observed that 95.5% cottonseed oil was converted to biodiesel. In the direct-alkaline trans-esterification process, 98.3% cottonseed oil was converted to biodiesel.

Determination of alpha-Tocopherol (vitamin E) in irradiated garlic by high performance liquid chromatography (HPLC)

International Nuclear Information System (INIS)

Rios, Magda Dias Goncalves; Penteado, Marilene de Vuono Camargo

2003-01-01

The effects of 60 Co ionizing radiations in doses of 0, 75, 100, 150, 200 and 250Gy on garlic, upon the α-tocopherol concentration were studied. The α-tocopherol contents were established by high performance liquid chromatography (HPLC), after direct hexane extraction from the garlic samples. The α-tocopherol was determined through normal phase column, and mobile phase was composed by hexane: iso-propyl alcohol (99:01 v/v), with 2mL/min flow rate and fluorescence detector. It is statistically shown that an irradiation dose of up to 150 Gy does not affect the garlic α-tocopherol content. (author)

Tocopherols and Tocotrienols in Common and Emerging Dietary Sources: Occurrence, Applications, and Health Benefits.

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Shahidi, Fereidoon; de Camargo, Adriano Costa

2016-10-20

Edible oils are the major natural dietary sources of tocopherols and tocotrienols, collectively known as tocols. Plant foods with low lipid content usually have negligible quantities of tocols. However, seeds and other plant food processing by-products may serve as alternative sources of edible oils with considerable contents of tocopherols and tocotrienols. Tocopherols are among the most important lipid-soluble antioxidants in food as well as in human and animal tissues. Tocopherols are found in lipid-rich regions of cells (e.g., mitochondrial membranes), fat depots, and lipoproteins such as low-density lipoprotein cholesterol. Their health benefits may also be explained by regulation of gene expression, signal transduction, and modulation of cell functions. Potential health benefits of tocols include prevention of certain types of cancer, heart disease, and other chronic ailments. Although deficiencies of tocopherol are uncommon, a continuous intake from common and novel dietary sources of tocopherols and tocotrienols is advantageous. Thus, this contribution will focus on the relevant literature on common and emerging edible oils as a source of tocols. Potential application and health effects as well as the impact of new cultivars as sources of edible oils and their processing discards are presented. Future trends and drawbacks are also briefly covered.

Tocopherols and Tocotrienols in Common and Emerging Dietary Sources: Occurrence, Applications, and Health Benefits

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Shahidi, Fereidoon; de Camargo, Adriano Costa

2016-01-01

Edible oils are the major natural dietary sources of tocopherols and tocotrienols, collectively known as tocols. Plant foods with low lipid content usually have negligible quantities of tocols. However, seeds and other plant food processing by-products may serve as alternative sources of edible oils with considerable contents of tocopherols and tocotrienols. Tocopherols are among the most important lipid-soluble antioxidants in food as well as in human and animal tissues. Tocopherols are found in lipid-rich regions of cells (e.g., mitochondrial membranes), fat depots, and lipoproteins such as low-density lipoprotein cholesterol. Their health benefits may also be explained by regulation of gene expression, signal transduction, and modulation of cell functions. Potential health benefits of tocols include prevention of certain types of cancer, heart disease, and other chronic ailments. Although deficiencies of tocopherol are uncommon, a continuous intake from common and novel dietary sources of tocopherols and tocotrienols is advantageous. Thus, this contribution will focus on the relevant literature on common and emerging edible oils as a source of tocols. Potential application and health effects as well as the impact of new cultivars as sources of edible oils and their processing discards are presented. Future trends and drawbacks are also briefly covered. PMID:27775605

Alkyl caffeates as antioxidants in O/W emulsions: Impact of emulsifier type and endogenous tocopherols

DEFF Research Database (Denmark)

Sørensen, Ann-Dorit Moltke; Villeneuve, Pierre; Jacobsen, Charlotte

2017-01-01

, the aim was to evaluate the impact of emulsifiers (Citrem and Tween80) and presence of endogenous tocopherols on the efficacies of caffeic acid and caffeates (C1–C20) as antioxidants in emulsions. Lipid oxidation was evaluated during storage and partitioning of caffeic acid and caffeates was estimated...... by measuring their concentrations in the aqueous phase. Partitioning of caffeic acid and caffeates was influenced by emulsifier type and the presence of endogenous tocopherols. Caffeic acid was the most efficient antioxidant in Citrem and Tween stabilized emulsions in the presence of endogenous tocopherol....... In contrast, for Tween stabilized emulsions, caffeic acid acted as a prooxidant and the evaluated caffeates acted as strong antioxidants in the absence of endogenous tocopherol. Thus, when endogenous tocopherol was present lipophilization of caffeic acid did not increase its efficacy as an antioxidant...

Vitamin E isomer δ-tocopherol enhances the efficiency of neural stem cell differentiation via L-type calcium channel.

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Deng, Sihao; Hou, Guoqiang; Xue, Zhiqin; Zhang, Longmei; Zhou, Yuye; Liu, Chao; Liu, Yanqing; Li, Zhiyuan

2015-01-12

The effects of the vitamin E isomer δ-tocopherol on neural stem cell (NSC) differentiation have not been investigated until now. Here we investigated the effects of δ-tocopherol on NSC neural differentiation, maturation and its possible mechanisms. Neonatal rat NSCs were grown in suspended neurosphere cultures, and were identified by their expression of nestin protein and their capacity for self-renewal. Treatment with a low concentration of δ-tocopherol induced a significant increase in the percentage of β-III-tubulin-positive cells. δ-Tocopherol also stimulated morphological maturation of neurons in culture. We further observed that δ-tocopherol stimulation increased the expression of voltage-dependent Ca(2+) channels. Moreover, a L-type specific Ca(2+) channel blocker verapamil reduced the percentage of differentiated neurons after δ-tocopherol treatment, and blocked the effects of δ-tocopherol on NSC differentiation into neurons. Together, our study demonstrates that δ-tocopherol may act through elevation of L-type calcium channel activity to increase neuronal differentiation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The establishment of tocopherol reference intervals for Hungarian adult population using a validated HPLC method.

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Veres, Gábor; Szpisjak, László; Bajtai, Attila; Siska, Andrea; Klivényi, Péter; Ilisz, István; Földesi, Imre; Vécsei, László; Zádori, Dénes

2017-09-01

Evidence suggests that decreased α-tocopherol (the most biologically active substance in the vitamin E group) level can cause neurological symptoms, most likely ataxia. The aim of the current study was to first provide reference intervals for serum tocopherols in the adult Hungarian population with appropriate sample size, recruiting healthy control subjects and neurological patients suffering from conditions without symptoms of ataxia, myopathy or cognitive deficiency. A validated HPLC method applying a diode array detector and rac-tocol as internal standard was utilized for that purpose. Furthermore, serum cholesterol levels were determined as well for data normalization. The calculated 2.5-97.5% reference intervals for α-, β/γ- and δ-tocopherols were 24.62-54.67, 0.81-3.69 and 0.29-1.07 μm, respectively, whereas the tocopherol/cholesterol ratios were 5.11-11.27, 0.14-0.72 and 0.06-0.22 μmol/mmol, respectively. The establishment of these reference intervals may improve the diagnostic accuracy of tocopherol measurements in certain neurological conditions with decreased tocopherol levels. Moreover, the current study draws special attention to the possible pitfalls in the complex process of the determination of reference intervals as well, including the selection of study population, the application of internal standard and method validation and the calculation of tocopherol/cholesterol ratios. Copyright © 2017 John Wiley & Sons, Ltd.

Relative bioefficacy of RRR-α-tocopherol versus all-rac-α-tocopherol in in vitro models

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Antonella Baldi

2015-11-01

Full Text Available The aim of this study was to evaluate the in vitro relative bioefficacy of RRR-α-tocopherol (RRR- α-T versus all-rac-α-tocopherol (all-rac-α-T in counteracting the cytotoxic effect induced by H2O2 in Bovine Mammary Epithelium – University of Vermont (BME-UV1 and Madin-Darby Canine Kidney (MDCK cells. The range of RRR- α-T and all-rac- α-T concentrations selected for the oxidative challenge experiments was 100µM - 1nM. To study the bioefficacy of RRR- α-T and all-rac- α-T, MTT and LDH tests were performed. Cells were pre-incubated for 3 h with  selected a-tocopherol concentrations and then exposed to increasing H2O2 concentrations ranging from 125 to 750µM for the following 24h. Concerning the cell viability, the pre-treatments with 100µM of RRR- α-T and 100µM all-rac-α-T were able to significantly (P<0.05 counteract the effect induced by 750 µM of H2O2 in BME-UV1. In MDCK the pre-treatment with 1nM of all-rac-α-T was able to significantly (P<0.05 reduce the effect of 125 and 150 mM H2O2. In MDCK cells, the pre-incubation with all-rac-α-T determines a significant reduction of the membrane damage, induced by 175 µM of H2O2. In conclusion, RRR-α-T and all-rac-α-T have shown the ability to counteract the oxidative effects of H2O2, however further investigation will help to better understand their specific mechanism of action in vitro.

Portulaca oleracea extract can inhibit nodule formation of colon cancer stem cells by regulating gene expression of the Notch signal transduction pathway.

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Jin, Heiying; Chen, Li; Wang, Shuiming; Chao, Deng

2017-07-01

To investigate whether Portulaca oleracea extract affects tumor formation in colon cancer stem cells and its chemotherapy sensitivity. In addition, to analyze associated genetic changes within the Notch signal transduction pathway. Serum-free cultures of colon cancer cells (HT-29) and HT-29 cancer stem cells were treated with the chemotherapeutic drug 5-fluorouracil to assess sensitivity. Injections of the stem cells were also given to BALB/c mice to confirm tumor growth and note its characteristics. In addition, the effect of different concentrations of P. oleracea extract was tested on the growth of HT-29 colon cancer cells and HT-29 cancer stem cells, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The effects of P. oleracea extract on the expression of β-catenin, Notch1, and Notch2 in the HT-29 cells were studied using reverse transcription polymerase chain reaction and Western blotting. The tumor volume of the HT29 cells was two times larger than that of HT29 cancer stem cells. Treatment with P. oleracea extract inhibited the proliferation of both HT-29 cancer cells and HT-29 cancer stem cells at doses from 0.07 to 2.25 µg/mL. Apoptosis of HT-29 cancer cells and HT-29 cancer stem cells was assessed by flow cytometry; it was enhanced by the addition of P. oleracea extract. Finally, treatment with P. oleracea extract significantly downregulated the expression of the Notch1 and β-catenin genes in both cell types. The results of this study show that P. oleracea extract inhibits the growth of colon cancer stem cells in a dose-dependent manner. Furthermore, it inhibits the expression of the Notch1 and β-catenin genes. Taken together, this suggests that it may elicit its effects through regulatory and target genes that mediate the Notch signal transduction pathway.

Caesium inhibits the colonization of Medicago truncatula by arbuscular mycorrhizal fungi

International Nuclear Information System (INIS)

Wiesel, Lea; Dubchak, Sergiy; Turnau, Katarzyna; Broadley, Martin R.; White, Philip J.

2015-01-01

Contamination of soils with radioisotopes of caesium (Cs) is of concern because of their emissions of harmful β and γ radiation. Radiocaesium enters the food chain through vegetation and the intake of Cs can affect the health of organisms. Arbuscular mycorrhizal (AM) fungi form mutualistic symbioses with plants through colonization of the roots and previous studies on the influence of AM on Cs concentrations in plants have given inconsistent results. These studies did not investigate the influence of Cs on AM fungi and it is therefore not known if Cs has a direct effect on AM colonization. Here, we investigated whether Cs influences AM colonization and if this effect impacts on the influence of Rhizophagus intraradices on Cs accumulation by Medicago truncatula. M. truncatula was grown with or without R. intraradices in pots containing different concentrations of Cs. Here, we present the first evidence that colonization of plants by AM fungi can be negatively affected by increasing Cs concentrations in the soil. Mycorrhizal colonization had little effect on root or shoot Cs concentrations. In conclusion, the colonization by AM fungi is impaired by high Cs concentrations and this direct effect of soil Cs on AM colonization might explain the inconsistent results reported in literature that have shown increased, decreased or unaffected Cs concentrations in AM plants. - Highlights: • Colonization of plants by arbuscular mycorrhizal fungi is negatively affected by increasing soil caesium concentrations. • Shoot caesium concentrations are not influenced by AM fungi at soil caesium concentrations above about 3 μg Cs kg −1 . • The direct effect of caesium on AM fungi might impact on the influence of AM fungi on Cs accumulation in plants. • This might explain the inconsistent results reported in literature on Cs accumulation in AM plants

Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer

International Nuclear Information System (INIS)

Nguyen, Anthony V; Martinez, Micaela; Stamos, Michael J; Moyer, Mary P; Planutis, Kestutis; Hope, Christopher; Holcombe, Randall F

2009-01-01

Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro. A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP) on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR) pre- and post-exposure to resveratrol/GP. Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03) activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001). These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line. These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted. NCT00256334

Recent advances in the determination of tocopherols in biological fluids: from sample pretreatment and liquid chromatography to clinical studies.

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Cervinkova, Barbora; Krcmova, Lenka Kujovska; Solichova, Dagmar; Melichar, Bohuslav; Solich, Petr

2016-04-01

Vitamin E comprises eight related compounds: α-, β-, γ-, δ-tocopherols and α-, β-, γ-, δ-tocotrienols. In the past, α-tocopherol has been the isomer that was studied most, and its anti-inflammatory and anti-proliferative effects have been described. Therefore, many prevention trials have investigated the effect of α-tocopherol on human health. Current research studies have also defined the important roles of other tocopherols, such as anti-inflammatory, anti-proliferative and cancer preventative effects. Knowledge of the individual tocopherols could help to understand their roles in various metabolic pathways. This review summarizes the recent trends in sample pretreatment, liquid chromatography and selected applications of the determination of tocopherols in various biological materials. The relationship between tocopherol isomers and serious diseases is also described. Graphical Abstract Article structure.

Serum tocopherol levels and vitamin E intake are associated with lung function in the normative aging study.

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Hanson, Corrine; Lyden, Elizabeth; Furtado, Jeremy; Campos, Hannia; Sparrow, David; Vokonas, Pantel; Litonjua, Augusto A

2016-02-01

The results of studies assessing relationships between vitamin E intake and status and lung function are conflicting. This study aimed to evaluate the effect of vitamin E intake and serum levels of tocopherol isoforms on lung function in a cross-sectional sample of 580 men from the Normative Aging Study, a longitudinal aging study. Regression models were used to look at associations of serum tocopherol isoform levels and vitamin E intake with lung function parameters after adjustment for confounders. Vitamin E intake was measured using a food frequency questionnaire and serum levels of γ, α, and δ-tocopherol levels were measured using high-performance liquid chromatography. After adjustment for potential confounders, serum γ-tocopherol had a significant inverse association with forced vital capacity (β = -0.10, p = 0.05). Alpha and δ-tocopherol were not associated with any lung function parameter. After classifying COPD status according to Global Initiative for Obstructive Lung Disease (GOLD) stage criteria, serum levels of δ-tocopherol were lower in participants with more severe COPD (p = 0.01). Serum levels of δ-tocopherol were also lower in participants with greater levels of smoking (p = 0.02). Both vitamin E intake (β = 0.03, p = 0.02; β = 0.03, p = 0.01) and use of vitamin E supplements (β = 0.05, p = 0.03; β = 0.06. p = 0.02) were positively associated with FEV1 and FVC, after adjusting for confounders. Subjects who took vitamin E supplements had significantly higher α-tocopherol levels (p tocopherol levels (p tocopherol and lung function. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Plasma zinc, vitamin B(12) and α-tocopherol are positively and plasma γ-tocopherol is negatively associated with Hb concentration in early pregnancy in north-west Bangladesh.

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Shamim, Abu Ahmed; Kabir, Alamgir; Merrill, Rebecca D; Ali, Hasmot; Rashid, Mahbubur; Schulze, Kerry; Labrique, Alain; West, Keith P; Christian, Parul

2013-08-01

The objective of the current analysis was to explore the association of multiple micronutrients with Hb concentration among pregnant women in a South Asian setting, a topic that has not been adequately explored. Sociodemographic, anthropometric and micronutrient status (plasma ferritin, transferrin receptor, retinol, a- and g-tocopherol, folate, vitamin B12, Zn) and Hb concentration were assessed at early pregnancy. The biochemical sub-study was nested within a double-blind, placebo-controlled, community-based vitamin A and b-carotene supplementation trial in rural north-western Bangladesh (JiVitA). All assessments were conducted before trial supplementation was initiated. A systematic sample of 285 women was selected from those enrolled in the biochemical sub-study. Seventeen per cent of women were mildly anaemic; moderate and severe anaemia was uncommon (2.1 %). a-Tocopherol, vitamin B12 and Zn deficiencies were common (43.5%, 19.7% and 14.7%, respectively); however, vitamin A, folate and Fe deficiencies were comparatively rare (7.4%, 2.8% and ,1%,respectively). Plasma Zn, vitamin B12 and a-tocopherol were positively associated and plasma g-tocopherol was negatively associated with Hb (P < 0.05) after adjustment for gestational age, inflammation status, season and nutritional status measured by mid-upper arm circumference. Among pregnant women in rural Bangladesh with minimal Fe deficiency, plasma Zn, vitamin B12, and a- and g-tocopherol concentrations were associated with Hb concentration. Appreciating the influence on Hb of micronutrients in addition to those with known associations with anaemia, such as Fe, folate, and vitamin A, is important when addressing anaemia in similar settings.

Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model

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BOUSSEROUEL, SOUAD; LE GRANDOIS, JULIE; GOSSÉ, FRANCINE; WERNER, DALAL; BARTH, STEPHAN W.; MARCHIONI, ERIC; MARESCAUX, JACQUES; RAUL, FRANCIS

2013-01-01

Shoots of white asparagus are a popular vegetable dish, known to be rich in many bioactive phytochemicals reported to possess antioxidant, and anti-inflammatory and antitumor activities. We evaluated the anticancer mechanisms of a methanolic extract of Asparagus officinalis L. shoots (Asp) on human colon carcinoma cells (SW480) and their derived metastatic cells (SW620), and Asp chemopreventive properties were also assessed in a model of colon carcinogenesis. SW480 and SW620 cell proliferation was inhibited by 80% after exposure to Asp (80 μg/ml). We demonstrated that Asp induced cell death through the activation of TRAIL DR4/DR5 death receptors leading to the activation of caspase-8 and caspase-3 and to cell apoptosis. By specific blocking agents of DR4/DR5 receptors we were able to prevent Asp-triggered cell death confirming the key role of DR4/DR5 receptors. We found also that Asp (80 μg/ml) was able to potentiate the effects of the cytokine TRAIL on cell death even in the TRAIL-resistant metastatic SW620 cells. Colon carcinogenesis was initiated in Wistar rats by intraperitoneal injections of azoxymethane (AOM), once a week for two weeks. One week after (post-initiation) rats received daily Asp (0.01%, 14 mg/kg body weight) in drinking water. After 7 weeks of Asp-treatment the colon of rats exhibited a 50% reduction of the number of preneoplastic lesions (aberrant crypt foci). In addition Asp induced inhibition of several pro-inflammatory mediators, in association with an increased expression of host-defense mediators. In the colonic mucosa of Asp-treated rats we also confirmed the pro-apoptotic effects observed in vitro including the activation of the TRAIL death-receptor signaling pathway. Taken together, our data highlight the chemopreventive effects of Asp on colon carcinogenesis and its ability to promote normal cellular homeostasis. PMID:23754197

Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells.

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Ya C Wu

Full Text Available Hydrogen sulfide (H(2S is a gaseous bacterial metabolite that reaches high levels in the large intestine. In the present study, the effect of H(2S on the proliferation of normal and cancerous colon epithelial cells was investigated. An immortalized colon epithelial cell line (YAMC and a panel of colon cancer cell lines (HT-29, SW1116, HCT116 were exposed to H(2S at concentrations similar to those found in the human colon. H(2S inhibited normal and cancerous colon epithelial cell proliferation as measured by MTT assay. The anti-mitogenic effect of H(2S was accompanied by G(1-phase cell cycle arrest and the induction of the cyclin-dependent kinase inhibitor p21(Cip. Moreover, exposure to H(2S led to features characteristic of autophagy, including increased formation of LC3B(+ autophagic vacuoles and acidic vesicular organelles as determined by immunofluorescence and acridine orange staining, respectively. Abolition of autophagy by RNA interference targeting Vps34 or Atg7 enhanced the anti-proliferative effect of H(2S. Further mechanistic investigation revealed that H(2S stimulated the phosphorylation of AMP-activated protein kinase (AMPK and inhibited the phosphorylation of mammalian target of rapamycin (mTOR and S6 kinase. Inhibition of AMPK significantly reversed H(2S-induced autophagy and inhibition of cell proliferation. Collectively, we demonstrate that H(2S inhibits colon epithelial cell proliferation and induces protective autophagy via the AMPK pathway.

Evaluation of a-tocopherol in virgin olive oil by a luminescent method

Energy Technology Data Exchange (ETDEWEB)

Escuderos, M. E.; Sayago, A.; Morales, M. T.; Aparicio, R.

2009-07-01

Natural fluorophores such as tocopherols are of great importance for the characterization and authentication of virgin olive oil. The band of the luminescent spectrum which is most accurately associated with the presence of a- tocopherol (380-420 nm) at {lambda}{sub e}xc = 350 nm was detected and its precision was evaluated once the analytical process was optimized. A virgin olive oil, cv. Cornicabra, was spiked with several quantities of a-tocopherol, from 25 mg/Kg to 1200mg/Kg, to build a ridge regression model (adjusted-R{sup 2} = 0.99) based on five wavelengths (370, 371, 378, 414 and 417 nm) which are attributed to the fluorescence of this compound. The tentative model was validated (adjusted-R2 = 0.87) with 8 samples of a virgin olive oil, cv. Picual, spiked with amounts of {alpha}-tocopherols ranging from 25 mg/kg to 250mg/kg. Finally, the model was successfully validated with 7 mono varietal virgin olive oils from various olive producing countries (adjusted - R{sup 2} = 0.92). (Author) 23 refs.

Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acid.

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Gessner, D K; Most, E; Schlegel, G; Kupczyk, K; Schwarz, F J; Eder, K

2015-12-01

This study was performed to investigate the hypothesis that supplementation of conjugated linoleic acid (CLA) changes the concentrations of retinol and tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a CLA-free rumen-protected control fat (control group, n = 20) or the same amount of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks 1, 3, 5, 8 and 11 of lactation) were analysed for retinol, α- and γ-tocopherol concentrations. Milk of cows supplemented with CLA had higher concentrations of retinol (+34%), α-tocopherol (+44%) and γ-tocopherol (+21%) than milk of control cows (p tocopherol and γ-tocopherol, respectively, p tocopherols, concentrations of thiobarbituric acid-reactive substances, determined in milk of week 5, were lower in cows of the CLA group than in control cows, indicative of a lower susceptibility of milk lipids to peroxidation. Plasma concentrations of retinol and α-tocopherol, determined at 1 and 5 weeks post-partum, were not different between the two groups of cows. In conclusion, this study shows that supplementing dairy cows with a moderate amount of CLA causes an increase of the concentrations of vitamins A and E in the milk and results in an increased output of those vitamins via milk. These effects might be beneficial with respect to the nutritional value of dairy products and the susceptibility of milk fat to oxidative deterioration. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Role of Endogenous and Exogenous Tocopherols in the Lipid Stability of Marine Oil Systems: A Review

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Guadalupe Miroslava Suárez-Jiménez

2016-11-01

Full Text Available In marine organisms primarily intended for human consumption, the quality of the muscle and the extracted oils may be affected by lipid oxidation during storage, even at low temperatures. This has led to a search for alternatives to maintain quality. In this sense, antioxidant compounds have been used to prevent such lipid deterioration. Among the most used compounds are tocopherols, which, due to their natural origin, have become an excellent alternative to prevent or retard lipid oxidation and maintain the quality of marine products. Tocopherols as antioxidants have been studied both exogenously and endogenously. Exogenous tocopherols are often used by incorporating them into plastic packaging films or adding them directly to fish oil. It has been observed that exogenous tocopherols incorporated in low concentrations maintain the quality of both muscle and the extracted oils during food storage. However, it has been reported that tocopherols applied at higher concentrations act as a prooxidant molecule, probably because their reactions with singlet oxygen may generate free radicals and cause the oxidation of polyunsaturated fatty acids in fish oils. However, when tocopherols are included in a fish diet (endogenous tocopherols, the antioxidant effect on the muscle lipids is more effective due to their incorporation into the membrane lipids, which can help extend the shelf life of seafood by reducing the lipid deterioration that occurs due to antioxidant synergy with other phenolic compounds used supplements in fish muscle. This review focuses on the most important studies in this field and highlights the potential of using tocopherols as antioxidants in marine oils.

Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth.

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Bell, Edward F; Hansen, Nellie I; Brion, Luc P; Ehrenkranz, Richard A; Kennedy, Kathleen A; Walsh, Michele C; Shankaran, Seetha; Acarregui, Michael J; Johnson, Karen J; Hale, Ellen C; Messina, Lynn A; Crawford, Margaret M; Laptook, Abbot R; Goldberg, Ronald N; Van Meurs, Krisa P; Carlo, Waldemar A; Poindexter, Brenda B; Faix, Roger G; Carlton, David P; Watterberg, Kristi L; Ellsbury, Dan L; Das, Abhik; Higgins, Rosemary D

2013-12-01

Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage. Ninety-three infants vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing. Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs. 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.

Role of Endogenous and Exogenous Tocopherols in the Lipid Stability of Marine Oil Systems: A Review

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Suárez-Jiménez, Guadalupe Miroslava; López-Saiz, Carmen María; Ramírez-Guerra, Hugo Enrique; Ezquerra-Brauer, Josafat Marina; Ruiz-Cruz, Saul; Torres-Arreola, Wilfrido

2016-01-01

In marine organisms primarily intended for human consumption, the quality of the muscle and the extracted oils may be affected by lipid oxidation during storage, even at low temperatures. This has led to a search for alternatives to maintain quality. In this sense, antioxidant compounds have been used to prevent such lipid deterioration. Among the most used compounds are tocopherols, which, due to their natural origin, have become an excellent alternative to prevent or retard lipid oxidation and maintain the quality of marine products. Tocopherols as antioxidants have been studied both exogenously and endogenously. Exogenous tocopherols are often used by incorporating them into plastic packaging films or adding them directly to fish oil. It has been observed that exogenous tocopherols incorporated in low concentrations maintain the quality of both muscle and the extracted oils during food storage. However, it has been reported that tocopherols applied at higher concentrations act as a prooxidant molecule, probably because their reactions with singlet oxygen may generate free radicals and cause the oxidation of polyunsaturated fatty acids in fish oils. However, when tocopherols are included in a fish diet (endogenous tocopherols), the antioxidant effect on the muscle lipids is more effective due to their incorporation into the membrane lipids, which can help extend the shelf life of seafood by reducing the lipid deterioration that occurs due to antioxidant synergy with other phenolic compounds used supplements in fish muscle. This review focuses on the most important studies in this field and highlights the potential of using tocopherols as antioxidants in marine oils. PMID:27886145

Humoral immune response of mice injected with tocopherol after exposure to X-radiation

International Nuclear Information System (INIS)

Roy, R.M.; Petrella, M.

1987-01-01

Serum haemagglutination (HA) titers have been determined for irradiated and non-irradiated mice responding to injection of two different concentrations of sheep red blood cells (SRBC) 24 to 48 hours after irradiation and immediate intraperitoneal injection of 2.5 mg DL alpha-tocopherol, the emulsifying vehicle, or saline. Mice maintained on tocopherol-deficient diets for 8 weeks post-weaning and those on regular diets exhibited increased IgG titers during peak response when injected with vitamin E. This partially alleviated the radiation-depression of the primary immune response induced by the smaller SRBC injection. This stimulatory effect was most significant in mice maintained on vitamin E-deficient diets. The HA titers of irradiated and non-irradiated mice maintained on normal rations were determined following a 10-fold increase in the SRBC inoculation. Antibody titer was greater following injection of the higher concentration of SRBC but post-irradiation injection of tocopherol immediately or 24 hours after irradiation did not enhance immune response. At the higher SRBC concentration maximum observed HA titers decreased with increasing dose of radiation; however, tocopherol had no significant dose-reducing effect. Tocopherol toxicity as manifested by depressed HA titers was observed occasionally in non-irradiated mice challenged with the higher concentration of SRBC

Tocotrienols and tocopherols in colored-grain wheat, tritordeum and barley.

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Lachman, Jaromír; Hejtmánková, Alena; Orsák, Matyáš; Popov, Marek; Martinek, Petr

2018-02-01

Colored-grain spring and winter wheat, spring tritordeum and barley (blue aleurone, purple pericarp, and yellow endosperm) from the harvests 2014 and 2015 were evaluated for tocol contents by HPLC-FD. Higher content of total tocols was found in spring wheat varieties compared with winter varieties. Four tocols (β-tocotrienol, α-tocotrienol, β-tocopherol, and α-tocopherol) were identified in wheat and tritordeum varieties. Dominant tocols in purple- and blue-grained wheat and yellow-grained tritordeum were α-tocopherol and β-tocotrienol, whereas spring barley varieties differed from wheat and tritordeum by high α-tocotrienol content. Tocol content was significantly affected by genotype and in a lesser extent in some varieties and lines also by rainfall and temperatures during crop year. Higher rainfall and lower temperatures caused in most varieties higher tocol contents. Purple- and blue-grained wheat lines with higher tocol, anthocyanin and phenolic acids with health benefits may be useful for breeding new varieties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer

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McDougall Gordon

2007-01-01

Full Text Available Abstract Background There is a probable association between consumption of fruit and vegetables and reduced risk of cancer, particularly cancer of the digestive tract. This anti-cancer activity has been attributed in part to anti-oxidants present in these foods. Raspberries in particular are a rich source of the anti-oxidant compounds, such as polyphenols, anthocyanins and ellagitannins. Methods A "colon-available" raspberry extract (CARE was prepared that contained phytochemicals surviving a digestion procedure that mimicked the physiochemical conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was assessed for anti-cancer properties in a series of in vitro systems that model important stages of colon carcinogenesis, initiation, promotion and invasion. Results The phytochemical composition of CARE was monitored using liquid chromatography mass spectrometry. The colon-available raspberry extract was reduced in anthocyanins and ellagitannins compared to the original raspberry juice but enriched in other polyphenols and polyphenol breakdown products that were more stable to gastrointestinal digestion. Initiation – CARE caused significant protective effects against DNA damage induced by hydrogen peroxide in HT29 colon cancer cells measured using single cell microgelelectrophoresis. Promotion – CARE significantly decreased the population of HT29 cells in the G1 phase of the cell cycle, effectively reducing the number of cells entering the cell cycle. However, CARE had no effect on epithelial integrity (barrier function assessed by recording the trans-epithelial resistance (TER of CACO-2 cell monolayers. Invasion – CARE caused significant inhibition of HT115 colon cancer cell invasion using the matrigel invasion assay. Conclusion The results indicate that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro.

Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

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Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

2016-01-19

Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

Effect of tocopherols incorporation on physical properties of LDPE,PP and blend film of LDPE/PP

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ZHU Xuntao

2014-12-01

Full Text Available The objectives of this study were to investigate the effects of added tocopherols and blending of different polymers on the film physical properties.Tocopherols (3 000 mg/kg were incorporate into low density polyethylene (LDPE,polypropylene (PP and a blend film of LDPE/PP (50/50 by extrusion process.Then films were evaluated to determine tocopherol recovery and physical properties.Results showed that extrusion did not significantly change film thermal properties (Tm,Tc and Tg as compared with synthetic polymer resin pellet (raw material.LDPE and PP did not seem to react with each other to form new polymers under the current extrusion conditions.Addition of tocopherol significantly changed film mechanical properties compared with control.The above results and other data seemed to support that polymer blending is a feasible approach for producing tocopherol containing packaging films.

γ-Oryzanol and tocopherol contents in residues of rice bran oil refining.

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Pestana-Bauer, Vanessa Ribeiro; Zambiazi, Rui C; Mendonça, Carla R B; Beneito-Cambra, Miriam; Ramis-Ramos, Guillermo

2012-10-01

Rice bran oil (RBO) contains significant amounts of the natural antioxidants γ-oryzanol and tocopherols, which are lost to a large degree during oil refining. This results in a number of industrial residues with high contents of these phytochemicals. With the aim of supporting the development of profitable industrial procedures for γ-oryzanol and tocopherol recovery, the contents of these phytochemicals in all the residues produced during RBO refining were evaluated. The samples included residues from the degumming, soap precipitation, bleaching earth filtering, dewaxing and deodorisation distillation steps. The highest phytochemical concentrations were found in the precipitated soap for γ-oryzanol (14.2 mg g(-1), representing 95.3% of total γ-oryzanol in crude RBO), and in the deodorisation distillate for tocopherols (576 mg 100 g(-1), representing 6.7% of total tocopherols in crude RBO). Therefore, among the residues of RBO processing, the deodorisation distillate was the best source of tocopherols. As the soap is further processed for the recovery of fatty acids, samples taken from every step of this secondary process, including hydrosoluble fraction, hydrolysed soap, distillation residue and purified fatty acid fraction, were also analyzed. The distillation residue left after fatty acid recovery from soap was found to be the best source of γ-oryzanol (43.1 mg g(-1), representing 11.5% of total γ-oryzanol in crude RBO). Copyright © 2012 Elsevier Ltd. All rights reserved.

The fatty acid and tocopherol constituents of the seed oil extracted from 21 grape varieties (Vitis spp.).

Science.gov (United States)

Sabir, Ali; Unver, Ahmet; Kara, Zeki

2012-07-01

Fatty acids and tocopherols in appropriate quantities are invaluable attributes that are desirable in seeds of agricultural products. Studies have generally focused on the evaluation of the oil and tocopherol components of oil crops. Recently, investigations revealed that the grape seed has robust potential in the production of healthy fatty acids as well as tocopherols. This study was thus conducted to determine the oil and tocopherol components of grape seeds, obtained from various grape cultivars of different species, including two rootstock varieties. The grape seed oil concentration of the studied varieties ranged from 7.3 to 22.4%. The determined fatty acid profiles of the genotypes conformed to the pattern described in the literature for grapes. Linoleic acid is the major component comprising 53.6-69.6% of the total, followed by oleic (16.2-31.2%), palmitic (6.9-12.9%) and stearic (1.44-4.69%). The oils of all the seeds analysed showed a preponderance of α-tocopherol (ranging from 260.5 to 153.1 mg kg⁻¹ oil extract). β-Tocopherol, γ-tocopherol and δ-tocopherol were also detected with the general means of 0.98, 22.2 and 0.92 mg kg⁻¹, respectively. Linoleic acid showed a significantly negative correlation with all the fatty acids analysed. The strongest negative correlation existed between linoleic and oleic acids (r = -0.834, P grape seed show great variation among the genotypes. Markedly higher proportions of linoleic acid with considerable amounts of tocopherols found in the oil samples suggest that grape seed is a good source for culinary, pharmaceutical and cosmetic uses. Copyright © 2012 Society of Chemical Industry.

TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol

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Zhiyu Zhang

2015-01-01

Full Text Available Among important components of American ginseng, protopanaxadiol (PPD showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound.

TRAIL pathway is associated with inhibition of colon cancer by protopanaxadiol.

Science.gov (United States)

Zhang, Zhiyu; Li, Zejuan; Wu, Xiaohui; Zhang, Chun-Feng; Calway, Tyler; He, Tong-Chuan; Du, Wei; Chen, Jianjun; Wang, Chong-Zhi; Yuan, Chun-Su

2015-01-01

Among important components of American ginseng, protopanaxadiol (PPD) showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial-mesenchymal transition in colon cancer cells.

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Chen, Shanwen; Zhu, Jing; Zuo, Shuai; Ma, Ju; Zhang, Junling; Chen, Guowei; Wang, Xin; Pan, Yisheng; Liu, Yucun; Wang, Pengyuan

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial-mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Simultaneous analysis of tert-butylhydroquinone, tert-butylquinone, butylated hydroxytoluene, 2-tert-butyl-4-hydroxyanisole, 3-tert-butyl-4-hydroxyanisole, α-tocopherol, γ-tocopherol, and δ-tocopherol in edible oils by normal-phase high performance liquid chromatography.

Science.gov (United States)

Li, Jun; Bi, Yanlan; Sun, Shangde; Peng, Dan

2017-11-01

A normal-phase high performance liquid chromatography method for the simultaneous determination of tert-butylhydroquinone, tert-butylquinone, butylated hydroxytoluene, 2-tert-butyl-4-hydroxyanisole, 3-tert-butyl-4-hydroxyanisole, α-tocopherol, γ-tocopherol, and δ-tocopherol in edible oils was investigated. A silica column was used to separate the analytes with the gradient elution. An ultraviolet-visible detector was set at dual wavelengths mode (280 and 310nm). The column temperature was 30°C. The analytes were directly extracted with methanol. Results showed that the normal-phase high performance liquid chromatography method performed well with wide liner ranges (0.10∼500.00μg/mL, R 2 >0.9998), low limits of detection and quantitation (below 0.40 and 1.21μg/mL, respectively), and good recoveries (81.38∼102.34% in soybean oils and 83.03∼100.79% in lard, respectively). The reduction of tert-butylquinone caused by the reverse-phase high performance liquid chromatography during the injection was avoided with the current normal-phase method. The two isomers of butylated hydroxyanisole can also be separated with good resolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coenzyme O*U1*UO, Alpha-Tocopherol and Free Cholesterol in HDL and LDL Fractions

DEFF Research Database (Denmark)

Johansen, Kurt; Theorell, Henning; Karlsson, Jan

1991-01-01

Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL......Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL...

Vasohibin-1 suppresses colon cancer

Science.gov (United States)

Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

2015-01-01

Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo. PMID:25797264

Vasohibin-1 suppresses colon cancer.

Science.gov (United States)

Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

2015-04-10

Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

Bio-discrimination of a-tocopherol stereoisomers in rearing and veal calves fed milk replacer supplemented with all-rac-a-tocopheryl acetate

DEFF Research Database (Denmark)

Dersjant-Li, Y.; Jensen, Søren Krogh; Bos, L.W.

2009-01-01

were taken at slaughter of the six veal calves in experiment 2. The distribution of different alpha-tocopherol stereoisomers in feed, plasma, and tissues was analyzed. In both experiments, it was observed that RRR-alpha-tocopherol was the dominant stereoisomer in plasma and tissues. The average...... vitamin E intake. Other 2R-alpha-tocopherol stereoisomers had lower utilization efficiency than RRR-alpha-tocopherol stereoisomer. 2S-alpha-tocopherol stereoisomers were basically not utilized by calves.......This study evaluated the biological discrimination of different alpha-tocopherol stereoisomers (i. e. RRR-, RRS-, RSR-, RSS- and the four 2S-alpha-tocopherols) from all-rac-alpha-tocopheryl acetate supplementation in milk replacer for rearing and veal calves respectively, in practical farming...

Remobilization of Phytol from Chlorophyll Degradation Is Essential for Tocopherol Synthesis and Growth of Arabidopsis

Science.gov (United States)

vom Dorp, Katharina; Hölzl, Georg; Plohmann, Christian; Eisenhut, Marion; Abraham, Marion

2015-01-01

Phytol from chlorophyll degradation can be phosphorylated to phytyl-phosphate and phytyl-diphosphate, the substrate for tocopherol (vitamin E) synthesis. A candidate for the phytyl-phosphate kinase from Arabidopsis thaliana (At1g78620) was identified via a phylogeny-based approach. This gene was designated VITAMIN E DEFICIENT6 (VTE6) because the leaves of the Arabidopsis vte6 mutants are tocopherol deficient. The vte6 mutant plants are incapable of photoautotrophic growth. Phytol and phytyl-phosphate accumulate, and the phytyl-diphosphate content is strongly decreased in vte6 leaves. Phytol feeding and enzyme assays with Arabidopsis and recombinant Escherichia coli cells demonstrated that VTE6 has phytyl-P kinase activity. Overexpression of VTE6 resulted in increased phytyl-diphosphate and tocopherol contents in seeds, indicating that VTE6 encodes phytyl-phosphate kinase. The severe growth retardation of vte6 mutants was partially rescued by introducing the phytol kinase mutation vte5. Double mutant plants (vte5 vte6) are tocopherol deficient and contain more chlorophyll, but reduced amounts of phytol and phytyl-phosphate compared with vte6 mutants, suggesting that phytol or phytyl-phosphate are detrimental to plant growth. Therefore, VTE6 represents the missing phytyl-phosphate kinase, linking phytol release from chlorophyll with tocopherol synthesis. Moreover, tocopherol synthesis in leaves depends on phytol derived from chlorophyll, not on de novo synthesis of phytyl-diphosphate from geranylgeranyl-diphosphate. PMID:26452599

Alpha-tocopherol transfer protein disruption confers resistance to malarial infection in mice

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Takeya Motohiro

2010-04-01

Full Text Available Abstract Background Various factors impact the severity of malaria, including the nutritional status of the host. Vitamin E, an intra and extracellular anti-oxidant, is one such nutrient whose absence was shown previously to negatively affect Plasmodium development. However, mechanisms of this Plasmodium inhibition, in addition to means by which to exploit this finding as a therapeutic strategy, remain unclear. Methods α-TTP knockout mice were infected with Plasmodium berghei NK65 or Plasmodium yoelii XL-17, parasitaemia, survival rate were monitored. In one part of the experiments mice were fed with a supplemented diet of vitamin E and then infected. In addition, parasite DNA damage was monitored by means of comet assay and 8-OHdG test. Moreover, infected mice were treated with chloroquine and parasitaemia and survival rate were monitored. Results Inhibition of α-tocopherol transfer protein (α-TTP, a determinant of vitamin E concentration in circulation, confers resistance to malarial infection as a result of oxidative damage to the parasites. Furthermore, in combination with the anti-malarial drug chloroquine results were even more dramatic. Conclusion Considering that these knockout mice lack observable negative impacts typical of vitamin E deficiency, these results suggest that inhibition of α-TTP activity in the liver may be a useful strategy in the prevention and treatment of malaria infection. Moreover, a combined strategy of α-TTP inhibition and chloroquine treatment might be effective against drug resistant parasites.

Protective effects of plasma alpha-tocopherols on the risk of inorganic arsenic-related urothelial carcinoma

International Nuclear Information System (INIS)

Chung, Chi-Jung; Pu, Yeong-Shiau; Chen, Ying-Ting; Su, Chien-Tien; Wu, Chia-Chang; Shiue, Horng-Sheng; Huang, Chao-Yuan; Hsueh, Yu-Mei

2011-01-01

Arsenic plays an important role in producing oxidative stress in cultured cells. To investigate the interaction between high oxidative stress and low arsenic methylation capacity on arsenic carcinogenesis, a case-control study was conducted to evaluate the relationship among the indices of oxidative stress, such as urinary 8-hydroxydeoxyquanine (8-OHdG), as well as plasma micronutrients and urinary arsenic profiles on urothelial carcinoma (UC) risk. Urinary 8-OHdG was measured using high-sensitivity enzyme-linked immunosorbent assay kits. The urinary arsenic species were analyzed using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Plasma micronutrient levels were analyzed using reversed-phase high-performance liquid chromatography. The present study showed a significant protective effect of plasma alpha-tocopherol on UC risk. Plasma alpha-tocopherol levels were significantly inversely related to urinary total arsenic concentrations and inorganic arsenic percentage (InAs%), and significantly positively related to dimethylarsinic acid percentage (DMA%). There were no correlations between plasma micronutrients and urinary 8-OHdG. Study participants with lower alpha-tocopherol and higher urinary total arsenic, higher InAs%, higher MMA%, and lower DMA% had a higher UC risk than those with higher alpha-tocopherol and lower urinary total arsenic, lower InAs%, lower MMA%, and higher DMA%. These results suggest that plasma alpha-tocopherol might modify the risk of inorganic arsenic-related UC. - Research Highlights: → Plasma alpha-tocopherol levels were significantly inversely related to UC risk. → There were no correlations between plasma micronutrients and urinary 8-OHdG. → People with lower alpha-tocopherol and higher total arsenic had increased UC risk.

Protective effects of plasma alpha-tocopherols on the risk of inorganic arsenic-related urothelial carcinoma

Energy Technology Data Exchange (ETDEWEB)

Chung, Chi-Jung [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Ying-Ting [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Huang, Chao-Yuan [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

2011-02-15

Arsenic plays an important role in producing oxidative stress in cultured cells. To investigate the interaction between high oxidative stress and low arsenic methylation capacity on arsenic carcinogenesis, a case-control study was conducted to evaluate the relationship among the indices of oxidative stress, such as urinary 8-hydroxydeoxyquanine (8-OHdG), as well as plasma micronutrients and urinary arsenic profiles on urothelial carcinoma (UC) risk. Urinary 8-OHdG was measured using high-sensitivity enzyme-linked immunosorbent assay kits. The urinary arsenic species were analyzed using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Plasma micronutrient levels were analyzed using reversed-phase high-performance liquid chromatography. The present study showed a significant protective effect of plasma alpha-tocopherol on UC risk. Plasma alpha-tocopherol levels were significantly inversely related to urinary total arsenic concentrations and inorganic arsenic percentage (InAs%), and significantly positively related to dimethylarsinic acid percentage (DMA%). There were no correlations between plasma micronutrients and urinary 8-OHdG. Study participants with lower alpha-tocopherol and higher urinary total arsenic, higher InAs%, higher MMA%, and lower DMA% had a higher UC risk than those with higher alpha-tocopherol and lower urinary total arsenic, lower InAs%, lower MMA%, and higher DMA%. These results suggest that plasma alpha-tocopherol might modify the risk of inorganic arsenic-related UC. - Research Highlights: {yields} Plasma alpha-tocopherol levels were significantly inversely related to UC risk. {yields} There were no correlations between plasma micronutrients and urinary 8-OHdG. {yields} People with lower alpha-tocopherol and higher total arsenic had increased UC risk.

Singlet oxygen autoxidation of vegetable oils: evidences for lack of synergy between β-carotene and tocopherols.

Science.gov (United States)

Smyk, Bogdan

2015-09-01

The synergy between β-carotene and tocopherols--antioxidants protecting oils from oxidation, was analyzed in a model system. The model used stripped borage and evening primrose oils. A chlorophyll extract, β-carotene and one of the tocopherols were added together or separately to the oils. Oil oxidation was initiated by singlet oxygen that was produced by chlorophylls irradiated with the use of a xenon lamp equipped with the cut-off 600 nm filter. Experiments were carried out at two mole ratios of tocopherols to β-carotene, i.e. at 1:1 and 23:1. Analyses were performed using absorption and fluorescence spectra in the UV+Vis region. The results demonstrated an antagonistic action of the antioxidants. The protective effect of unsaturated fatty acids was significantly better in the case of β-carotene compared to the tocopherols. Furthermore, tocopherols were less effective in protecting the oils in the presence of β-carotene than without it. Copyright © 2015 Elsevier Ltd. All rights reserved.

Frying stability of high oleic sunflower oils as affected by composition of tocopherol isomers and linoleic acid content.

Science.gov (United States)

Aladedunye, Felix; Przybylski, Roman

2013-12-01

The influence of linoleic acid content and tocopherol isomeric composition on the frying performance of high oleic sunflower oil was evaluated during a 14-day restaurant style frying operation. At equal linoleic acid content, no significant difference was observed between high oleic sunflower oil containing only α-tocopherol and the sample containing a mixture of α-, γ-, and δ-isomers as measured by the amount of total polar components, oligomers, anisidine value, and free fatty acids. On the contrary, at similar tocopherol isomeric composition, high oleic sunflower oil containing lower amount of linoleic acid showed superior frying stability compared to the sample with a higher content of linoleic acid, suggesting that the frying performance of high oleic sunflower oil is dictated primarily by the level of linoleic acid, with the tocopherol isomeric composition of the oil having no significant influence. In all oil samples, the loss of γ-tocopherol was higher than the corresponding loss of α-tocopherol. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tocoferois e tocotrienois em óleos vegetais e ovos Tocopherols and tocotrienols in vegetable oils and eggs

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Michele Guinaz

2009-01-01

Full Text Available The distribution and content of vitamin E isomers was investigated in vegetable oils and raw and cooked egg yolk in commercial restaurants. The analysis of the eight vitamin E isomers was carried out by High Performance Liquid Chromatography (HPLC with fluorescence detection. The tocopherol and tocotrienol composition of foods varied considerably. Tocopherols were detected in greater quantity and frequency. The α-tocopherol predominated in egg yolks and olive oil while γ-tocopherol was found in high quantities in soybean and canola oils. Cooking did not cause major losses for most of the vitamin E isomers in egg yolks.

Synergistic antioxidant activity of milk sphingomyeline and its sphingoid base with α-tocopherol on fish oil triacylglycerol.

Science.gov (United States)

Shimajiri, Junki; Shiota, Makoto; Hosokawa, Masashi; Miyashita, Kazuo

2013-08-21

The effects of milk phospholipids (PLs), sphingolipids (SLs), and their sphingoid backbone on the oxidation of fish oil triacylglycerol (TAG) were examined with or without α-tocopherol. All compounds had little effect on the TAG oxidation in the absence of α-tocopherol. On the other hand, they could act synergistically with α-tocopherol. The highest synergistic activity was shown by sphingoid bases, followed by sphingomyelin (SPM) and other amine-containing PLs and SLs. This result showed that the synergistic activity increased with an increasing concentration of amine group of PLs, SLs, or sphingoid bases in the reaction mixture. The comparison of changes in α-tocopherol content in fish oil TAG and tricaprylin suggested that antioxidant compounds would be formed from the amine group and the lipid oxidation products in a mild oxidation condition controlled by α-tocopherol.

α-Tocopherol incorporation in mitochondria and microsomes upon supranutritional vitamin E supplementation

DEFF Research Database (Denmark)

Lauridsen, Charlotte; Jensen, Søren Krogh

2012-01-01

Vitamin E (α-tocopherol) is a major lipid-soluble chain-breaking antioxidant in humans and mammals and plays an important role in normal development and physiology. The localization of α-tocopherol within the highly unsaturated phospholipid bilayer of cell membranes provides a means of controlling...... cellular compartments is important in order to maintain oxidative stability of the membrane-bound lipids and prevent damage from the reactive oxygen species. Many studies regarding mitochondrial disease and dysfunction have been performed in relation to deficiency of vitamin E and other antioxidants...... with antioxidants on their incorporation into mitochondria and other cellular membranes. The purpose of this review is therefore to briefly summarize experimental data performed with dietary vitamin E treatments in relation to the deposition of α-tocopherol in mitochondria and microsomes....

Protective Effects of α-Tocopherol on ABR Threshold Shift in Rabbits Exposed to Noise and Carbon Monoxide.

Science.gov (United States)

Motallebi Kashani, Masoud; Mortazavi, Seyyed Bagher; Khavanin, Ali; Allameh, Abdolamir; Mirzaee, Ramezan; Akbari, Mehdi

2011-01-01

Noise induced hearin gloss (NIHL) is one of the most important occupational disease world wide. NIHL has been found potentiate by simultaneous carbon monoxide (CO) exposure. Free radicals have been implicated in cochlear damage resulted from the exposure to noise and due to the CO hypoxia. This study examined whether α-tocopherol administration , as a free radical scavenger, causes the attenuation of auditory brainstem response (ABR) threshold shifts resulting from noise exposure and noise plus CO exposure. Forty-two rabbits were divided in to seven groups including control, noise + saline, noise + CO + saline, noise + α-tocopherol, noise + CO + α-tocopherol , CO + α-tocopherol and α-tocopherol alone. ABR was assessed before exposure, 1 hand 14 days post exposure. The administration of 50 mg/Kg of α-tocopherol prior, following and post exposure to noise or noise plus CO recovered permanent ABR threshold shift at 1 and KHz almost to the baseline and provided significant attenuation in permanent ABR threshold shift at 4 and 8 KHz in subject swhich were exposed to noise but it did not block the potentiating of threshold elevation by CO exposure (extra threshold loss by combined exposure) at 4 and 8 KHz. α Tocopherol provides protective effect against the hearing loss resulting from noise exposure and simultaneous exposure to noise plus CO.

Alfa-tocopherol and beta-carotene in roughages and milk in organic dairy herds

DEFF Research Database (Denmark)

Mogensen, Lisbeth; Kristensen, Troels; Søegaard, Karen

2012-01-01

as stored silage. As an average of several sampling times, roughage α-tocopherol and β-carotene contents (mg per kg DM) during the period when the roughage was fed were, respectively, 30 and 21 in grass–clover silage, 13 and 8 in maize wholecrop silage and 28 and 9 in cereal wholecrop silage. Daily intake...... of α-tocopherol was 876 mg per cow–431 mg from roughages, 89 mg from concentrates and 356 mg from a vitamin supplement. Milk yield was 25.9 kg energy-corrected milk (ECM) per cow per day with α-tocopherol and β-carotene contents (μg/ml) of 0.82 and 0.17. The study additionally showed the following...

A first-generation physiologically based pharmacokinetic (PBPK) model of alpha-tocopherol in human influenza vaccine adjuvant.

Science.gov (United States)

Tegenge, Million A; Mitkus, Robert J

2015-04-01

Alpha (α)-tocopherol is a component of a new generation of squalene-containing oil-in-water (SQ/W) emulsion adjuvants that have been licensed for use in certain influenza vaccines. Since regulatory pharmacokinetic studies are not routinely required for influenza vaccines, the in vivo fate of this vaccine constituent is largely unknown. In this study, we constructed a physiologically based pharmacokinetic (PBPK) model for emulsified α-tocopherol in human adults and infants. An independent sheep PBPK model was also developed to inform the local preferential lymphatic transfer and for the purpose of model evaluation. The PBPK model predicts that α-tocopherol will be removed from the injection site within 24h and rapidly transfer predominantly into draining lymph nodes. A much lower concentration of α-tocopherol was estimated to peak in plasma within 8h. Any systemically absorbed α-tocopherol was predicted to accumulate slowly in adipose tissue, but not in other tissues. Model evaluation and uncertainty analyses indicated acceptable fit, with the fraction of dose taken up into the lymphatics as most influential on plasma concentration. In summary, this study estimates the in vivo fate of α-tocopherol in adjuvanted influenza vaccine, may be relevant in explaining its immunodynamics in humans, and informs current regulatory risk-benefit analyses. Published by Elsevier Inc.

Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations.

Science.gov (United States)

de Azeredo, Vilma B; Trugo, Nadia M F

2008-02-01

We determined the concentrations of retinol, carotenoids, and tocopherols in breast milk of adolescents and evaluated their associations with plasma levels and with maternal characteristics (period of lactation, body mass index, age of menarche, and years postmenarche). This was a single cross-sectional survey of retinol, carotenoid, and tocopherol composition of milk and plasma of lactating adolescent mothers (n = 72; 30-120 d postpartum) attending public daycare clinics in Rio de Janeiro, Brazil. Milk and plasma components were analyzed by high-performance liquid chromatography. Nutrient concentrations (micromoles per liter, mean +/- SE) in plasma and milk were, respectively, retinol 2.1 +/- 0.5 and 0.62 +/- 0.44, beta-carotene 0.18 +/- 0.19 and 0.016 +/- 0.017, alpha-carotene 0.05 +/- 0.04 and 0.0035 +/- 0.002, lutein plus zeaxanthin 0.15 +/- 0.11 and 0.025 +/- 0.024, lycopene 0.1 +/- 0.11 and 0.016 +/- 0.025, alpha-tocopherol 10.8 +/- 5.3 and 2.7 +/- 1.8, gamma-tocopherol 2.6 +/- 2.3 and 0.37 +/- 0.15. The milk/plasma molar ratios of retinol and tocopherols were two times higher than those of carotenoids. Significant correlations (P milk and plasma nutrient levels were observed for beta-carotene (r = 0.41), alpha-carotene (r = 0.60), and lutein plus zeaxanthin (r = 0.57), but not for lycopene, retinol, and tocopherols. Nutrient concentrations in plasma and in milk were not associated with the maternal characteristics investigated. Concentrations of the nutrients studied, especially retinol and alpha-tocopherol, in mature milk of lactating adolescents were, in general, lower than in milk of adult lactating women. Milk concentrations were associated with plasma concentrations only for beta-carotene, alpha-carotene, and lutein plus zeaxanthin.

EGFR regulation of colon cancer stem-like cells during aging and in response to the colonic carcinogen dimethylhydrazine.

Science.gov (United States)

Nautiyal, Jyoti; Du, Jianhua; Yu, Yingjie; Kanwar, Shailender S; Levi, Edi; Majumdar, Adhip P N

2012-04-01

One of the most consistent pathological conditions in the gastrointestinal tract with advancing age is malignancy, particularly gastrointestinal cancers, the incidence of which increases sharply with aging. Although the reasons for the age-related rise in colorectal cancer are not fully understood, we hypothesize that aging increases susceptibility of the colon to carcinogen(s)/toxicant(s), leading to an increase in cancer stem-like cells (CSLCs) that express cancer stem cell markers, in the colonic mucosa. The current study demonstrates that aging is associated with increased expression of several colon CSLC markers [CD44, CD166, and aldehyde dehydrogenase 1 (ALDH-1)] and a higher proportion of cells expressing these markers. Aging is also accompanied by increased expression of miR-21 in colon. These increases are further increased in response to the colonic carcinogen dimethylhydrazine (DMH). Aging is also associated with increased tyrosine-phosphorylated epidermal growth factor receptor (EGFR). Inhibition of EGFR using the EGFR inhibitor cetuximab abrogated the age-related increase in CD166 and ALDH-1 as well as miRNA (miR)-21. Our results provide new evidence that aging and DMH are associated with increases in CSLC biomarkers and miR21, each of which have been linked to colorectal cancer. EGFR inhibition attenuates these changes, indicating a role for EGFR in age- and mutagen-associated changes in CSLCs.

Fatty acid, carotenoid and tocopherol compositions of 20 Canadian lentil cultivars and synergistic contribution to antioxidant activities.

Science.gov (United States)

Zhang, Bing; Deng, Zeyuan; Tang, Yao; Chen, Peter; Liu, Ronghua; Ramdath, D Dan; Liu, Qiang; Hernandez, Marta; Tsao, Rong

2014-10-15

Understanding the profile of lipophilic phytochemicals in lentils is necessary to better understand the health benefits of lentils. The fatty acid, carotenoid and tocopherol compositions and antioxidant activities of the lipophilic extracts of 20 lentil cultivars (10 red and 10 green) were therefore examined. Lentils contained 1.52-2.95% lipids, of which 77.5-81.7% were unsaturated essential fatty acids. Total tocopherols ranged from 37 to 64μg/g DW, predominantly γ-tocopherol (96-98% of the tocopherol content), followed by δ- and α-tocopherol. trans-Lutein was the primary and major carotenoid (64-78%) followed by trans-zeaxanthin (5-13%). Carotenoids and tocopherols showed weak correlation with 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity (r=0.4893 and 0.3259, respectively), but good correlation when combined (r=0.6688), suggesting they may act synergistically. Carotenoids were found to contribute the most to the strong antioxidant activity measured by photochemiluminescence (PCL) assay. Results from this study contribute to the development of lentil cultivars and related functional foods with increased health benefits. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Cell Growth Inhibition Effect of DsiRNA Vectorised by Pectin-Coated Chitosan-Graphene Oxide Nanocomposites as Potential Therapy for Colon Cancer

Directory of Open Access Journals (Sweden)

Haliza Katas

2017-01-01

Full Text Available Colonic-targeted drug delivery system is widely explored to combat colon-related diseases such as colon cancer. Dicer-substrate small interfering RNA (DsiRNA has been explored for cancer therapy due to its potency in targeting specific gene of interest. However, its application is limited by rapid degradation and poor cellular uptake. To address this, chitosan-graphene oxide (CS-GO nanocomposite was used to deliver DsiRNA effectively into cells. Additionally, pectin was used as compatibilization agent to allow specific delivery to the colon and protect the nanocomposites from the harsh environment in the stomach and small intestine. CS-GO-DsiRNA nanocomposites were prepared by electrostatic interaction between CS and GO prior to coating with pectin. The mean particle size of CS-GO-DsiRNA-pectin nanocomposites was 554.5±124.6 nm with PDI and zeta potential of 0.47±0.19 and −10.7±3.0 mV, respectively. TEM analysis revealed smooth and spherical shape of CS-GO-DsiRNA nanocomposites and the shape became irregular after pectin coating. FTIR analysis further confirmed the successful formation of CS-GO-DsiRNA-pectin nanocomposites. Furthermore, the nanocomposites were able to entrap high amount of DsiRNA (% entrapment efficiency of 92.6±3.9% with strong binding efficiency. CS-GO-DsiRNA-pectin nanocomposites also selectively inhibited cell growth of colon cancer cell line (Caco-2 cells and were able to decrease VEGF level significantly. In a nutshell, pectin-coated DsiRNA-loaded CS-GO nanocomposites were successfully developed and they have a great potential to deliver DsiRNA to the colon effectively.

Antioxidant Activities of á-Tocopherol, Herbalox and ...

African Journals Online (AJOL)

This study was carried out to determine possible synergism and antagonism in blends of natural and synthetic antioxidants for protection of palm olein at high temperatures. Three primary antioxidants: (±)-á-tocopherol (Vitamin E), Rosemary extract (Herbalox) and butylated hydroxytoluene (BHT) were used in a mixture ...

Silencing of the hTERT gene by shRNA inhibits colon cancer SW480 cell growth in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Ai-Qun Liu

Full Text Available Human telomerase reverse transcriptase (hTERT is the key enzyme responsible for synthesizing and maintaining the telomeres on the ends of chromosomes, and it is essential for cell proliferation. This has made hTERT a focus of oncology research and an attractive target for anticancer drug development. In this study, we designed a small interfering RNA (siRNA targeting the catalytic subunit of hTERT and tested its effects on the growth of telomerase-positive human colon carcinoma SW480 cells in vitro, as well as on the tumorigenicity of these cells in nude mice. Transient and stable transfection of hTERT siRNA into colon cancer SW480 cells suppressed hTERT expression, reduced telomerase activity and inhibited cell growth and proliferation. Knocking down hTERT expression in SW480 tumors xenografted into nude mice significantly slowed tumor growth and promoted tumor cell apoptosis. Our results suggest that hTERT is involved in carcinogenesis of human colon carcinoma, and they highlight the therapeutic potential of a hTERT knock-down approach.

Chlorophyll Synthase under Epigenetic Surveillance Is Critical for Vitamin E Synthesis, and Altered Expression Affects Tocopherol Levels in Arabidopsis.

Science.gov (United States)

Zhang, Chunyu; Zhang, Wei; Ren, Guodong; Li, Delin; Cahoon, Rebecca E; Chen, Ming; Zhou, Yongming; Yu, Bin; Cahoon, Edgar B

2015-08-01

Chlorophyll synthase catalyzes the final step in chlorophyll biosynthesis: the esterification of chlorophyllide with either geranylgeranyl diphosphate or phytyl diphosphate (PDP). Recent studies have pointed to the involvement of chlorophyll-linked reduction of geranylgeranyl by geranylgeranyl reductase as a major pathway for the synthesis of the PDP precursor of tocopherols. This indirect pathway of PDP synthesis suggests a key role of chlorophyll synthase in tocopherol production to generate the geranylgeranyl-chlorophyll substrate for geranylgeranyl reductase. In this study, contributions of chlorophyll synthase to tocopherol formation in Arabidopsis (Arabidopsis thaliana) were explored by disrupting and altering expression of the corresponding gene CHLOROPHYLL SYNTHASE (CHLSYN; At3g51820). Leaves from the homozygous chlysyn1-1 null mutant were nearly devoid of tocopherols, whereas seeds contained only approximately 25% of wild-type tocopherol levels. Leaves of RNA interference lines with partial suppression of CHLSYN displayed marked reductions in chlorophyll but up to a 2-fold increase in tocopherol concentrations. Cauliflower mosaic virus35S-mediated overexpression of CHLSYN unexpectedly caused a cosuppression phenotype at high frequencies accompanied by strongly reduced chlorophyll content and increased tocopherol levels. This phenotype and the associated detection of CHLSYN-derived small interfering RNAs were reversed with CHLSYN overexpression in rna-directed rna polymerase6 (rdr6), which is defective in RNA-dependent RNA polymerase6, a key enzyme in sense transgene-induced small interfering RNA production. CHLSYN overexpression in rdr6 had little effect on chlorophyll content but resulted in up to a 30% reduction in tocopherol levels in leaves. These findings show that altered CHLSYN expression impacts tocopherol levels and also, show a strong epigenetic surveillance of CHLSYN to control chlorophyll and tocopherol synthesis. © 2015 American Society of

The influence of dibutyryl adenosine cyclic monophosphate on cell proliferation in the epithelium of the jejunal crypts, the colonic crypts and in colonic carcinomata of rat.

Science.gov (United States)

Tutton, P J; Barkla, D H

1980-01-01

1. Cell proliferation in the jejunal crypts, the colonic crypts and in dimethylhydrazine (DMH)-induced adenocarcinomata of rat colon was measured using a stathmokinetic technique. 2. Dibutryl cyclic adneosine monophosphate (dibutyryl cAMP) was found to inhibit cell proliferation in colonic crypts and in colonic adenocarcinomata. 3. Dibutryl cAMP at very high doses was found to inhibit jejunal crypt cell proliferation but at lower doses was found to accelerate jejunal crypt cell proliferation. 4. Neither bilateral adrenalectomy nor chemical sympathectomy was found to abolish the ability of dibutryl cAMP to stimulate jejunal crypt cell proliferation. 5. The present results are difficult to interpret in terms of known hormonal influences on cell proliferation in the tissues examined and of established actions, of these hormones on cyclic nucleotide metabolism in other tissues.

Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation on Tumor-Associated Endothelial Cells Leads to Treatment of Orthotopic Human Colon Cancer in Nude Mice

Directory of Open Access Journals (Sweden)

Takamitsu Sasaki

2007-12-01

Full Text Available The purpose of our study was to determine whether the dual inhibition of epidermal growth factor receptor (EGFR and vascular endothelial growth factor receptor (VEGFR signaling pathways in tumor-associated endothelial cells can inhibit the progressive growth of human colon carcinoma in the cecum of nude mice. SW620CE2 human colon cancer cells growing in culture and orthotopically in the cecum of nude mice expressed a high level of transforming growth factor alpha (TGF-α and vascular endothelial growth factor (VEGF but were negative for EGFR, human epidermal growth factor receptor 2 (HER2, VEGFR. Double immunofluorescence staining revealed that tumorassociated endothelial cells expressed EGFR, VEGFR2, phosphorylated EGFR (pEGFR, phosphorylated VEGFR (pVEGFR. Treatment of mice with either 7H-pyrrolo [2,3-d]-pyrimidine lead scaffold (AEE788; an inhibitor of EGFR and VEGFR tyrosine kinase or CPT-11 as single agents significantly inhibited the growth of cecal tumors (P < .01; this decrease was even more pronounced with AEE788 combined with CPT-11 (P < .001. AEE788 alone or combined with CPT-11 also inhibited the expression of pEGFR and pVEGFR on tumor-associated endothelial cells, significantly decreased vascularization and tumor cell proliferation, increased the level of apoptosis in both tumorassociated endothelial cells and tumor cells. These data demonstrate that targeting EGFR and VEGFR signaling on tumor-associated endothelial cells provides a viable approach for the treatment of colon cancer.

Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression.

Science.gov (United States)

Zakraoui, Ons; Marcinkiewicz, Cezary; Aloui, Zohra; Othman, Houcemeddine; Grépin, Renaud; Haoues, Meriam; Essafi, Makram; Srairi-Abid, Najet; Gasmi, Ammar; Karoui, Habib; Pagès, Gilles; Essafi-Benkhadir, Khadija

2017-01-01

Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Periplocin from Cortex periplocae inhibits cell growth and down-regulates survivin and c-myc expression in colon cancer in vitro and in vivo via beta-catenin/TCF signaling.

Science.gov (United States)

Zhao, Lianmei; Shan, Baoen; Du, Yanyan; Wang, Mingxia; Liu, Lihua; Ren, Feng-Zhi

2010-08-01

Cancer of the colon and rectum is the third most commonly diagnosed cancer and accounts for approximately 10% of all cancer-related deaths. Although surgical resection or radiotherapy are potentially curative for localized disease, advanced colon cancer is currently associated with poor prognosis. Therefore, the development of a new and effective chemotherapeutic agent is required to target critical pathways to induce responsiveness of colon cancer cells to death signals. Dysregulation of the beta-catenin/TCF pathway plays a central role in early activities of colorectal carcinogenesis. In this study, human colon cancer SW480 cells were used to investigate the effect of CPP (periplocin from Cortex periplocae) on the modulation of the beta-catenin/TCF signaling pathway. Our research results showed that CPP caused a dose- and time-dependent inhibition of cell growth as assessed by MTT assay and an induction in apoptosis as measured by flow cytometry and transmission electron microscopy. Furthermore, the CPP- treated cells were characterized by a decreased expression of beta-catenin protein in the total cell lysates and cytosolic and nuclear extracts. This expression alleviates the binding activity of T-cell factor (Tcf) complexes to its specific DNA-binding sites. Thus, the protein expression of the downstream elements survivin and c-myc was down-regulated. To determine the precise inhibitory mechanisms involved, further in-depth in vivo studies of CPP are warranted. In conclusion, our data suggest that CPP wields a multi-prong strategy to target the beta-catenin/Tcf signaling pathway, leading to the induction of apoptosis and inhibition of growth of colon cancer cells in vitro and in vivo. Therefore, CPP may become a potential agent against colon cancer.

Predictors of adipose tissue tocopherol and toenail selenium levels in nine countries : the EURAMIC study

NARCIS (Netherlands)

Virtanen, S.M.; Veer, P. van 't; Kok, F.; Kardinaal, A.F.M.; Aro, A.; for the EURAMIC Study Group

1996-01-01

Objective: To evaluate the levels of adipose tissue alpha-tocopherol, gamma-tocopherol, and toenail selenium and their determinants. Design: Control subjects from multicentre case-control study on antioxidants, myocardial infarction and cancer of the breast. Subjects and setting: 686 male and 339

The effect of gamma 60Co radiation on the decomposition and dimers formation of γ-tocopherol

International Nuclear Information System (INIS)

Jasinska-Stepniak, A.

1995-01-01

A standard of γ-tocopherol (MERCK) was irradiated with the doses up to 20 kGy. The irradiation was performed using tocopherol 'in substantia' and dissolved in ethanol and benzene. Radiolytic decomposition and formation of dimers were determined using the Emmerie-Engel procedure. The yield of decomposition of γ-tocopherol does not indicate its particular sensitivity to the radiation treatments, since the most frequent G-values of chemical food components are 2-3. The concentration remained the detection level. (author)

Profile of Fatty Acids, Amino Acids, Carotenoid Total, and α-Tocopherol from Flying Fish Eggs

Directory of Open Access Journals (Sweden)

Aulia Azka

2015-12-01

Full Text Available Flying fish are found in waters of eastern Indonesia, which until now is still limited informationabout nutritional content. The purpose of this research was determine the composition offatty acids, amino acids, total carotenoids, α-tocopherol flying fish eggs (Hyrundicthys sp..The composition of fatty acid was measured by gas chromatography (GC, while amino acids,total carotenoids, α-tocopherol was measured by High performanced Liquid Chromatography(HPLC. Egg contained 22 fatty acids such as saturated fatty acid 29.71%, monounsaturated fattyacid 7.86%, and polysaturated fatty acid 13.64%. The result showed that eggs flying fish contained17 amino acids, such as essential amino acid 14.96% and non-essential amino acids 20.27%. Eggscontained a total carotenoid of 245.37 ppm. α-tocopherol content of flying fish eggs by 1.06 ppm.Keywords: Amino acids, carotenoid total, fatty acid, flying fish egg, α-tocopherol

De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

DEFF Research Database (Denmark)

Lavrsen, Kirstine; Dabelsteen, Sally; Vakhrushev, Sergey Y

2018-01-01

Aberrant expression of O-glycans is a hallmark of epithelial cancers. Mucin type O-glycosylation is initiated by a large family of UDP-GalNAc:polypeptide N-acetyl-galactosaminyltransferases (GalNAc-Ts), that target different proteins and are differentially expressed in cells and organs. Here we...... investigated the expression patterns of all of the GalNAc-Ts in colon cancer by analysing transcriptomic data. We found that GalNAc-T6 was highly upregulated in colon adenocarcinomas but absent in normal-appearing adjacent colon tissue. The results were verified by immunohistochemistry, suggesting that Gal......NAc-T6 plays a role in colon carcinogenesis. To investigate the function of GalNAc-T6 in colon cancer, we used precise gene targeting to produce isogenic colon cancer cell lines with a knockout/-rescue system for GalNAc-T6. GalNAc-T6 expression was associated with a cancer-like, dysplastic growth pattern...

Post-synthetic modification of MIL-101(Cr) with pyridine for high-performance liquid chromatographic separation of tocopherols.

Science.gov (United States)

Yang, Fang; Yang, Cheng-Xiong; Yan, Xiu-Ping

2015-05-01

Effective separation of tocopherols is challenging and significant due to their structural similarity and important biological role. Here we report the post-synthetic modification of metal-organic framework (MOF) MIL-101(Cr) with pyridine for high-performance liquid chromatographic (HPLC) separation of tocopherols. Baseline separation of four tocopherols was achieved on a pyridine-grafted MIL-101(Cr) packed column within 10 min using hexane/isopropanol (96:4, v/v) as the mobile phase at a flow rate of 0.5 mL min(-1). The pyridine-grafted MIL-101(Cr) packed column gave high column efficiency (85,000 plates m(-1) for δ-tocopherol) and good precision (0.2-0.3% for retention time, 1.8-3.4% for peak area, 2.6-2.7% for peak height), and also offered much better performance than unmodified MIL-101(Cr) and commercial amino-bonded silica packed column for HPLC separation of tocopherols. The results not only show the promising application of pyridine-grafted MIL-101(Cr) as a novel stationary phase for HPLC separation of tocopherols, but also reveal a facile post-modification of MOFs to expand the application of MOFs in separation sciences. Copyright © 2015 Elsevier B.V. All rights reserved.

Tocopherols, Tocomonoenols, and Tocotrienols in Oils of Costa Rican Palm Fruits: A Comparison between Six Varieties and Chemical versus Mechanical Extraction.

Science.gov (United States)

Irías-Mata, Andrea; Stuetz, Wolfgang; Sus, Nadine; Hammann, Simon; Gralla, Katrin; Cordero-Solano, Aracelly; Vetter, Walter; Frank, Jan

2017-08-30

Palm oil is one of the richest sources of tocotrienols and may contain other non-tocopherol vitamin E congeners. The vitamin E profiles of fully ripened fruit mesocarp of three Elaeis guineensis, two Elaeis oleifera, and one hybrid O × G palm fruit genotypes from Costa Rica were analyzed by high-performance liquid chromatography with fluorescence detection and gas chromatography-mass spectrometry after mechanical extraction by a screw press and chemical extraction with hexane. γ-Tocotrienol, α-tocotrienol, and α-tocopherol were the most abundant tocochromanols, while other tocopherols (β-tocopherol, γ-tocopherol, and δ-tocopherol) and α-tocomonoenol were detected at minor concentrations. Significant differences in vitamin E profiles between genotypes were observed, and the variety E. oleifera Quepos (CB9204) had by far the highest content of total tocotrienols (890 μg/g of oil) and total vitamin E (892 μg/g of oil). Chemical extraction with hexane afforded up to 2.5-fold higher vitamin E yields than screw press extraction. α-Tocomonoenol co-eluted with γ-tocopherol in reversed-phase high-performance liquid chromatography analyses and is a possible source of error in the quantification of γ-tocopherol in foods.

Airway fungal colonization compromises the immune system allowing bacterial pneumonia to prevail.

Science.gov (United States)

Roux, Damien; Gaudry, Stéphane; Khoy-Ear, Linda; Aloulou, Meryem; Phillips-Houlbracq, Mathilde; Bex, Julie; Skurnik, David; Denamur, Erick; Monteiro, Renato C; Dreyfuss, Didier; Ricard, Jean-Damien

2013-09-01

To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats. Experimental animal investigation. University research laboratory. Pathogen-free male Wistar rats weighing 250-275 g. Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats. C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia. C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.

Neutrophil superoxide-anion generating capacity in chronic smoking: effect of long-term alpha-tocopherol therapy

NARCIS (Netherlands)

Tits, van L.; Waart, de F.; Hak-Lemmers, H.L.M.; Graaf, de J.; Demacker, P.N.; Stalenhoef, A.F.

2003-01-01

We investigated whether long-term alpha-tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 21 pack years of smoking) to treatment with placebo (n = 64) or alpha-tocopherol (400 IU

Novel simple process for tocopherols selective recovery from vegetable oils by adsorption and desorption with an anion-exchange resin.

Science.gov (United States)

Hiromori, Kousuke; Shibasaki-Kitakawa, Naomi; Nakashima, Kazunori; Yonemoto, Toshikuni

2016-03-01

A novel and simple low-temperature process was used to recover tocopherols from a deodorizer distillate, which is a by-product of edible oil refining. The process consists of three operations: the esterification of free fatty acids with a cation-exchange resin catalyst, the adsorption of tocopherols onto an anion-exchange resin, and tocopherol desorption from the resin. No degradation of tocopherols occurred during these processes. In the tocopherol-rich fraction, no impurities such as sterols or glycerides were present. These impurities are commonly found in the product of the conventional process. This novel process improves the overall recovery ratio and the mass fraction of the product (75.9% and 51.0wt%) compared with those in the conventional process (50% and 35wt%). Copyright © 2015 Elsevier Ltd. All rights reserved.

Methods for efficient analysis of tocopherols, tocotrienols and their metabolites in animal samples with HPLC-EC

Directory of Open Access Journals (Sweden)

Mao-Jung Lee

2018-01-01

Full Text Available Tocopherols and tocotrienols, collectively known as vitamin E, have received a great deal of attention because of their interesting biological activities. In the present study, we reexamined and improved previous methods of sample preparation and the conditions of high-performance liquid chromatography for more accurate quantification of tocopherols, tocotrienols and their major chain-degradation metabolites. For the analysis of serum tocopherols/tocotrienols, we reconfirmed our method of mixing serum with ethanol followed by hexane extraction. For the analysis of tissue samples, we improved our methods by extracting tocopherols/tocotrienols directly from tissue homogenate with hexane. For the analysis of total amounts (conjugated and unconjugated forms of side-chain degradation metabolites, the samples need to be deconjugated by incubating with β-glucuronidase and sulfatase; serum samples can be directly used for the incubation, whereas for tissue homogenates a pre-deproteination step is needed. The present methods are sensitive, convenient and are suitable for the determination of different forms of vitamin E and their metabolites in animal and human studies. Results from the analysis of serum, liver, kidney, lung and urine samples from mice that had been treated with mixtures of tocotrienols and tocopherols are presented as examples.

The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

International Nuclear Information System (INIS)

Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling; Shen, Jie

2015-01-01

In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administration of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions. - Highlights: • AR-42 is anti-proliferative against primary/established colon cancer cells. • AR-42 induces significant apoptotic death in primary/established colon cancer cells. • Ceramide production mediates AR-42-induced cytotoxicity in colon cancer cells. • AR-42 oral administration potently inhibits SW-620 xenograft growth in SCID mice

The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

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Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling [Department of Clinical Laboratory, Tongren Hospital, Shanghai (China); Shen, Jie, E-mail: tongrensj163@163.com [Department of Administrative, Tongren Hospital, No. 786 Yuyuan Road, Changning District, Shanghai (China)

2015-08-07

In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administration of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions. - Highlights: • AR-42 is anti-proliferative against primary/established colon cancer cells. • AR-42 induces significant apoptotic death in primary/established colon cancer cells. • Ceramide production mediates AR-42-induced cytotoxicity in colon cancer cells. • AR-42 oral administration potently inhibits SW-620 xenograft growth in SCID mice.

Ubiquitin-specific peptidase 22 inhibits colon cancer cell invasion by suppressing the signal transducer and activator of transcription 3/matrix metalloproteinase 9 pathway.

Science.gov (United States)

Ao, Ning; Liu, Yanyan; Bian, Xiaocui; Feng, Hailiang; Liu, Yuqin

2015-08-01

Colon cancer is associated with increased cell migration and invasion. In the present study, the role of ubiquitin-specific peptidase 22 (USP22) in signal transducer and activator of transcription 3 (STAT3)-mediated colon cancer cell invasion was investigated. The messenger RNA levels of STAT3 target genes were measured by reverse transcription-quantitative polymerase chain reaction, following USP22 knockdown by RNA interference in SW480 colon cancer cells. The matrix metalloproteinase 9 (MMP9) proteolytic activity and invasion potential of SW480 cells were measured by zymography and Transwell assay, respectively, following combined USP22 and STAT3 short interfering (si)RNA treatment or STAT3 siRNA treatment alone. Similarly, a cell counting kit-8 assay was used to detect the proliferation potential of SW480 cells. The protein expression levels of USP22, STAT3 and MMP9 were detected by immunohistochemistry in colon cancer tissue microarrays (TMAs) and the correlation between USP22, STAT3 and MMP9 was analyzed. USP22/STAT3 co-depletion partly rescued the MMP9 proteolytic activity and invasion of SW480 cells, compared with that of STAT3 depletion alone. However, the proliferation of USP22/STAT3si-SW480 cells was decreased compared with that of STAT3si-SW480 cells. USP22 expression was positively correlated with STAT3 and MMP9 expression in colon cancer TMAs. In conclusion, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3/MMP9 signaling pathway.

Quality changes during frozen storage of blue shrimp (Litopenaeus stylirostris with antioxidant, α-tocopherol, under different conditions

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Adriana Zulema Valencia-Perez

2015-06-01

Full Text Available Fresh blue shrimp (Litopenaeus stylirostris muscle was stored with antioxidants under different conditions: ANTIOX 2%, packed in bilayer film of polyamide-low density polyethylene film (PA-LDPE with 2% α-tocopherol; ANTIOX 4%, packed in PA-LDPE film with 4% α-tocopherol; and ANTIOX-GLAZED, samples stored glazed with 2% α-tocopherol. Shrimps packed in PA-LDPE without α-tocopherol were used as CONTROL. All samples were stored at –20 °C for 120 days. As compared to the CONTROL, the shrimp stored with the antioxidant showed lower lipid oxidation (0.10-0.14 vs 1.58 mgMA/kg of muscle, lost less firmness and astaxanthin content. ANTIOX 2% and ANTIOX-GLAZED showed the lowest concentrations of formaldehyde (0.081-0.083 μM/g. There were no significant differences in color and sensory properties, but differences in the integrity of the muscle fibers were observed. The treatments with α-tocopherol maintained the shrimp muscle quality during frozen storage. However, no significant differences were found between these treatments.

Increased humoral immunity by DNA vaccination using an alpha-tocopherol-based adjuvant

DEFF Research Database (Denmark)

Karlsson, Ingrid; Borggren, Marie; Nielsen, Jens

2017-01-01

approaches. We tested whether the emulsion-based and alpha-tocopherol containing adjuvant Diluvac Forte® has the ability to enhance the immunogenicity of a naked DNA vaccine (i.e., plasmid DNA). As a model vaccine, we used plasmids encoding both a surface-exposed viral glycoprotein (hemagglutinin......) and an internal non-glycosylated nucleoprotein in the Th1/Th2 balanced CB6F1 mouse model. The naked DNA (50 µg) was premixed at a 1:1 volume/volume ratio with Diluvac Forte®, an emulsion containing different concentrations of alpha-tocopherol, the emulsion alone or endotoxin-free phosphate-buffered saline (PBS......). The animals received two intracutaneous immunizations spaced 3 weeks apart. When combined with Diluvac Forte® or the emulsion containing alpha-tocopherol, the DNA vaccine induced a more potent and balanced immunoglobulin G (IgG)1 and IgG2c response, and both IgG subclass responses were significantly enhanced...

Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

NARCIS (Netherlands)

Erk, M.J. van; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, P.J. van; Aarts, J.M.M.J.G.; Ommen, B. van

2004-01-01

Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

NARCIS (Netherlands)

Erk, van M.J.; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, van P.J.; Aarts, J.M.M.J.G.; Ommen, van B.

2004-01-01

Background: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

NARCIS (Netherlands)

Van Erk, Marjan J; Teuling, Eva; Staal, Yvonne C. M.; Huybers, Sylvie; Van Bladeren, Peter J; Aarts, Jac MMJG; Van Ommen, Ben

2004-01-01

BACKGROUND: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an

Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells.

Science.gov (United States)

Zeng, Huawei; Trujillo, Olivia N; Moyer, Mary P; Botnen, James H

2011-01-01

Sulforaphane (SFN) is a naturally occurring chemopreventive agent; the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon cancer and normal cells. In this study, we demonstrated that SFN (15 μmol/L) exposure (72 h) inhibited cell proliferation by up to 95% in colon cancer cells (HCT116) and by 52% in normal colon mucosa-derived (NCM460) cells. Our data also showed that SFN exposure (5 and 10 μmol/L) led to the reduction of G1 phase cell distribution and an induction of apoptosis in HCT116 cells, but to a much lesser extent in NCM460 cells. Furthermore, the examination of mitogen-activated protein kinase (MAPK) signaling status revealed that SFN upregulated the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) in NCM460 cells but not in HCT116 cells. In contrast, SFN enhanced the phosphorylation of stress-activated protein kinase (SAPK) and decreased cellular myelocytomatosis oncogene (c-Myc) expression in HCT116 cells but not NCM460 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic signaling in HCT116 cells may play a critical role in SFN's stronger potential of inhibiting cell proliferation in colon cancer cells than in normal colon cells. Copyright © 2011, Taylor & Francis Group, LLC

Tocopherol isomer pattern in serum and stool of human following consumption of black currant seed press residue administered in whole grain bread.

Science.gov (United States)

Helbig, Dorit; Wagner, Andreas; Schubert, Rainer; Jahreis, Gerhard

2009-12-01

Serum gamma-tocopherol is thought to be associated with human health. The dietary influence of tocopherol and fibre-rich black currant seed press residue on serum and stool tocopherol concentration was investigated in a controlled human intervention study. Thirty-six women consumed bread enriched with black currant press residue (4 weeks). The resultant faecal and serum tocopherol concentrations were compared with those after a period consuming control bread without press residue and a normal baseline diet. Fibre intake and excretion, antioxidant capacity (TEAC), and vitamin C concentrations in serum and urine were also determined. Samples were obtained with a 5-day standardised diet at the end of each period. The press residue bread lead to significantly increased beta-, gamma-, delta- and total tocopherol intake, serum alpha-, beta-, gamma- and total tocopherol concentration (with and without lipid adjustment), fibre intake and urinary vitamin C concentration compared to control bread (Pconsumption could be due to a presumed interruption of the enzymatic tocopherol degradation mechanism by bread constituents.

PGE2-induced colon cancer growth is mediated by mTORC1

International Nuclear Information System (INIS)

Dufour, Marc; Faes, Seraina; Dormond-Meuwly, Anne; Demartines, Nicolas; Dormond, Olivier

2014-01-01

Highlights: • PGE 2 activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE 2 induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE 2 induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E 2 (PGE 2 ) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE 2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE 2 -induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE 2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE 2 EP 4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE 2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE 2 -induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE 2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE 2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth

Investigations of the inhibitory effects of tocopherol (vitamin E) on free radical deterioration of cellular membranes

Science.gov (United States)

Richardson, D.

1975-01-01

The inhibitory effects are investigated of d,1-alpha-tocopherol and d,1-alpha-tocopheryl acetate on the free radical deterioration of cellular membranes. The level of toxicity of d,1-alpha-tocopherol and d,1-alpha-tocopheryl acetate in mice is determined.

Feasibility for improving phytonutrient content in vegetable crops using conventional breeding strategies: case study with carotenoids and tocopherols in sweet corn and broccoli.

Science.gov (United States)

Ibrahim, Khalid E; Juvik, John A

2009-06-10

Among vegetables, sweet corn ( Zea mays L.) and broccoli ( Brassica oleracea L. ssp. italica) are important sources of dietary carotenoids and tocopherols. Because medical evidence suggests that carotenoid and tocopherol health-promoting activity acts in a dose-dependent manner, conventional breeding to develop elite sweet corn and broccoli germplasm with enhanced levels of these phytochemicals will potentially promote health among the consuming public. This investigation includes the quantitative analysis of carotenoid and tocopherol contents of 41 corn and 24 broccoli genotypes grown in multiple environments (years and seasons in one location) to partition the variation into genetic, environment, and genotype by environment interaction (GxE) components and measure the phenotypic stability of genotypes for these phytochemicals. The primary carotenoids and tocopherols in corn were lutein and gamma-tocopherol (65 and 73% of total carotenoid and tocopherol, respectively), whereas beta-carotene and alpha-tocopherol were dominant in broccoli (65 and 79% of total carotenoid and tocopherol, respectively). Partitioning of the variance indicated that genetic differences among the genotypes averaged for the primary compounds in corn (lutein, zeaxanthin, and alpha- and gamma-tocopherol) and broccoli (beta-carotene, lutein, and alpha- and gamma-tocopherol) accounted for the largest proportion of the variation (67 and 55% of total phenotypic variation averaged across the phytochemicals in sweet corn and broccoli, respectively). Stability analysis identified several corn (IL451b sh2 and IL2027-8 sh2) and broccoli ('Pirate' and 'Baccus') genotypes with relatively high mean concentrations for the various carotenoids and tocopherols that were comparatively stable across seasons and years. The results of this investigation suggest that sweet corn and broccoli germplasm with enhanced concentrations of carotenoids and tocopherols can be developed using conventional breeding protocols.

Chlorophyll Synthase under Epigenetic Surveillance Is Critical for Vitamin E Synthesis, and Altered Expression Affects Tocopherol Levels in Arabidopsis1[OPEN

Science.gov (United States)

Zhang, Chunyu; Zhang, Wei; Ren, Guodong; Li, Delin; Cahoon, Rebecca E.; Chen, Ming; Zhou, Yongming; Yu, Bin

2015-01-01

Chlorophyll synthase catalyzes the final step in chlorophyll biosynthesis: the esterification of chlorophyllide with either geranylgeranyl diphosphate or phytyl diphosphate (PDP). Recent studies have pointed to the involvement of chlorophyll-linked reduction of geranylgeranyl by geranylgeranyl reductase as a major pathway for the synthesis of the PDP precursor of tocopherols. This indirect pathway of PDP synthesis suggests a key role of chlorophyll synthase in tocopherol production to generate the geranylgeranyl-chlorophyll substrate for geranylgeranyl reductase. In this study, contributions of chlorophyll synthase to tocopherol formation in Arabidopsis (Arabidopsis thaliana) were explored by disrupting and altering expression of the corresponding gene CHLOROPHYLL SYNTHASE (CHLSYN; At3g51820). Leaves from the homozygous chlysyn1-1 null mutant were nearly devoid of tocopherols, whereas seeds contained only approximately 25% of wild-type tocopherol levels. Leaves of RNA interference lines with partial suppression of CHLSYN displayed marked reductions in chlorophyll but up to a 2-fold increase in tocopherol concentrations. Cauliflower mosaic virus35S-mediated overexpression of CHLSYN unexpectedly caused a cosuppression phenotype at high frequencies accompanied by strongly reduced chlorophyll content and increased tocopherol levels. This phenotype and the associated detection of CHLSYN-derived small interfering RNAs were reversed with CHLSYN overexpression in rna-directed rna polymerase6 (rdr6), which is defective in RNA-dependent RNA polymerase6, a key enzyme in sense transgene-induced small interfering RNA production. CHLSYN overexpression in rdr6 had little effect on chlorophyll content but resulted in up to a 30% reduction in tocopherol levels in leaves. These findings show that altered CHLSYN expression impacts tocopherol levels and also, show a strong epigenetic surveillance of CHLSYN to control chlorophyll and tocopherol synthesis. PMID:26048882

Early detection of doxorubicin-induced cariotoxocity and its prevention by alpha-tocopherol

International Nuclear Information System (INIS)

Ajmal, K.; Khan, B.T.

2014-01-01

To detect doxorubicin-induced myocardial injury by quantitative estimation of cardiospecific protein, Cardiac Troponin I (cTnI) at early stage and to evaluate the cardioprotective effects of Tocopherol. Study Design: Labbased randomized controlled in-vivo study in rabbits. Place and Duration of Study: Department of Pharmacology in collaboration with Pathology department, Army Medical College Rawalpindi, Pakistan from Jan 2012 to Dec 2012. Material and Methods: Eighteen healthy male adult rabbits were used. Cardiotoxicity was induced by single intravenous injection of 12 mg /kg of doxorubicin in a group of rabbits, control group was treated with normal saline only and the rabbits of third group were pretreated with Tocopherol 200 mg/kg of body weight for ten days before injection of doxorubicin 12mg/kg. Results: Doxorubicin produced severe cardiotoxicity confirmed by markedly raised serum levels of cTnI, CK-MB, LDH and grade 3 necrosis of the heart issue in rabbits. The pre-treatment with Tocopherol resulted in improved serum levels of cTnI and the histological picture of heart tissue. Conclusions: The quantitative cTnI estimation for detection of cardiotoxicity at subclinical level can lead to significant economic impact in management of cancer patients because the troponin-negative subjects can be excluded from long term cardiac monitoring programs, which require high cost imaging techniques. Furthermore, the outcome of most potent and widely used doxorubicin chemotherapy can be made successful with the concurrent use of alpha-Tocopherol. (author)

Optimization conditions of samples saponification for tocopherol analysis.

Science.gov (United States)

Souza, Aloisio Henrique Pereira; Gohara, Aline Kirie; Rodrigues, Ângela Claudia; Ströher, Gisely Luzia; Silva, Danielle Cristina; Visentainer, Jesuí Vergílio; Souza, Nilson Evelázio; Matsushita, Makoto

2014-09-01

A full factorial design 2(2) (two factors at two levels) with duplicates was performed to investigate the influence of the factors agitation time (2 and 4 h) and the percentage of KOH (60% and 80% w/v) in the saponification of samples for the determination of α, β and γ+δ-tocopherols. The study used samples of peanuts (cultivar armadillo), produced and marketed in Maringá, PR. The factors % KOH and agitation time were significant, and an increase in their values contributed negatively to the responses. The interaction effect was not significant for the response δ-tocopherol, and the contribution of this effect to the other responses was positive, but less than 10%. The ANOVA and response surfaces analysis showed that the most efficient saponification procedure was obtained using a 60% (w/v) solution of KOH and with an agitation time of 2 h. Copyright © 2014 Elsevier Ltd. All rights reserved.

Temperature influence during seed filling on tocopherol concentration in a traditional sunflower hybrid

Directory of Open Access Journals (Sweden)

Nolasco, S.M.

2007-06-01

Full Text Available The effect of night temperature during short periods in seed filling on oil tocopherol content and tocopherol/linoleic acid ratio was investigated in a traditional sunflower hybrid. Seeds were sown in the field at Balcarce on the 3rd and 22nd of November. In each experiment, treatments in which night temperature was increased at three consecutive periods of 200 °C day (base temperature: 6 °C were applied.Tocopherol concentration was reduced when night temperature was increased early in seed filling. Such an increase could be attributed to a correlative increase in the daily average temperature, as no differences in tocopherol concentration were found when plants were cultivated in growth chambers under different day/night temperature but at the same daily average temperature. Temperature affected tocopherol concentration mainly by affecting the oil weight per seed.The tocopherol/linoleic acid ratio was not affected by temperature.Se investigó el efecto de la temperatura durante períodos cortos en el llenado de las semillas sobre la concentración de tocoferoles y la relación tocoferoles/ácido linoleico en un híbrido tradicional de girasol. Se realizó una siembra en campo en Balcarce el 3 y el 22 de noviembre. En cada experimento, se aplicaron tratamientos donde se incrementó la temperatura de la noche en tres períodos consecutivos de 200 °C día (temperatura base: 6 °C. La concentración de tocoferoles disminuyó cuando se incrementó la temperatura de la noche temprano durante el llenado de las semillas. Dicho aumento puede ser atribuido a aumentos en la temperatura media diaria ya que no se observaron diferencias en la concentración de tocoferoles cuando se cultivaron plantas en cámaras de crecimiento con distinta temperatura nocturna y la misma temperatura media diaria. La temperatura afectó la concentración de tocoferoles principalmente al afectar el peso de aceite por semilla. La relación tocoferoles/ �

EFFECTS OF L-ASCORBIC ACID AND ALPHA-TOCOPHEROL ON BIOCHEMICAL PARAMETERS OF SWIMMING-INDUCED OXIDATIVE STRESS IN SERUM OF GUINEA PIGS.

Science.gov (United States)

Bursać-Mitrović, Marija; Milovanović, Dragan R; Mitić, Radoslav; Jovanović, Danijela; Sovrlić, Miroslav; Vasiljević, Perica; Tomović, Jovica; Manojlović, Nedeljko

2016-01-01

The purpose of this study is to determine the effect of L-ascorbic acid and alpha-tocopherol as well as combination of these vitamins with or without exposure to physical exercise on intensity of lipid peroxidation, activity of xanthine oxidase, activity of total antioxidative system, concentration of glutathione, and activity of catalase in the serum of guinea pigs. The experimental measurements of intensity of lipid peroxidation, activity of xanthine oxidase, activity of total antioxidative system, concentration of glutathione, and activity of catalase were done in the serum of guinea pigs. The animals were exposed to the test load to achieve exhaustion and the test was terminated when the animal for the third time to sink into the water. The results of this study demonstrated that endurance exercise of guinea pigs induced oxidative stress response in terms of increased lipid peroxidation and activity of xanthine oxidase in the serum of experimental animals. Our study investigated the antioxidant activity of L-ascorbic acid and alpha-tocopherol also measuring three protective markers in the serum: total antioxidant activity, content of glutathione and activity of catalase. The results obtained show that the vitamins influence the concentrations of above mentioned biochemical parameters, which points out their protective effect of swimming-induced oxidative stress. Single or combined administration of L-ascorbic acid and alpha-tocopherol caused significant inhibition of these markers indicating the important antioxidant activity of the vitamins. Results lead to conclude that the combined treatments with vitamins with or without exposure to physical exercise showed the clear synergistic effect..

Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation.

Science.gov (United States)

Zeng, Huawei; Briske-Anderson, Mary; Wu, Min; Moyer, Mary P

2012-01-01

Methylselenol is hypothesized to be a critical selenium metabolite for anticancer action, and differential chemopreventive effects of methylselenol on cancerous and noncancerous cells may play an important role. In this study, the submicromolar concentrations of methylselenol were generated by incubating methionase with seleno-L methionine, and colon-cancer-derived HCT-116 cells and noncancerous colon NCM460 cells were exposed to methylselenol. Methylselenol exposure inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase and an induction of apoptosis in HCT116, but to a much lesser extent in NCM460 colon cells. Similarly, the examination of mitogen-activated protein kinase (MAPK) and cellular myelocytomatosis oncogene (c-Myc) signaling status revealed that methylselenol inhibited the phosphorylation of extracellular-regulated kinase1/2 and p38 mitogen-activated protein kinase and the expression of c-Myc in HCT116 cells, but also to a lesser extent in NCM460 cells. The other finding is that methylselenol inhibits sarcoma kinase phosphorylation in HCT116 cells. In contrast, methylselenol upregulated the phosphorylation of sarcoma and focal adhesion kinase survival signals in the noncancerous NCM460 cells. Collectively, methylselenol's stronger potential of inhibiting cell proliferation/survival signals in the cancerous HCT116 cells when compared with that in noncancerous NCM460 cells may partly explain the potential of methylselenol's anticancer action.

Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

International Nuclear Information System (INIS)

Dydensborg, Anders Bondo; Teller, Inga C; Groulx, Jean-François; Basora, Nuria; Paré, Fréderic; Herring, Elizabeth; Gauthier, Rémy; Jean, Dominique; Beaulieu, Jean-François

2009-01-01

Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking. In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line. Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc. The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin

Thiamin, riboflavin and alpha-tocopherol retention in processed and stored irradiated pork

International Nuclear Information System (INIS)

Fox, J.B. Jr.; Lakritz, L.; Thayer, D.W.

1997-01-01

Combination treatments for preservation of irradiated pork were investigated with respect to vitamin loss. Ground pork was prepared under nitrogen and packaged in anaerobic foil. The samples were enzyme denatured by heating before and after irradiation, then cooked and stored. Irradiation resulted in thiamin loss, but neither riboflavin nor alpha-tocopherol was affected. Neither thiamin nor riboflavin was affected by heat denaturation, cooking or storage, but heating and cooking increased the measured alpha-tocopherol. The lack of loss of the vitamins was attributed to the exclusion of oxygen

DFT/B3LYP study of tocopherols and chromans antioxidant action energetics

International Nuclear Information System (INIS)

Klein, Erik; Lukes, Vladimir; Ilcin, Michal

2007-01-01

Gas-phase reaction enthalpies related to the individual steps of three phenolic antioxidants action mechanisms - hydrogen atom transfer (HAT), single-electron transfer-proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) for four tocopherols and seven chromans - were calculated using DFT/B3LYP method. For α-tocopherol, one of the chromans and phenol, reaction enthalpies in water were computed. In comparison to gas phase, water causes severe changes in the energetics of studied compounds antioxidant action. From the thermodynamic point of view, entering SPLET mechanism represents the most probable process in water

DFT/B3LYP study of tocopherols and chromans antioxidant action energetics

Energy Technology Data Exchange (ETDEWEB)

Klein, Erik [Institute of Physical Chemistry and Chemical Physics, Slovak University of Technology, Radlinskeho 9, SK-812 37 Bratislava (Slovakia)], E-mail: erik.klein@stuba.sk; Lukes, Vladimir; Ilcin, Michal [Institute of Physical Chemistry and Chemical Physics, Slovak University of Technology, Radlinskeho 9, SK-812 37 Bratislava (Slovakia)

2007-07-09

Gas-phase reaction enthalpies related to the individual steps of three phenolic antioxidants action mechanisms - hydrogen atom transfer (HAT), single-electron transfer-proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) for four tocopherols and seven chromans - were calculated using DFT/B3LYP method. For {alpha}-tocopherol, one of the chromans and phenol, reaction enthalpies in water were computed. In comparison to gas phase, water causes severe changes in the energetics of studied compounds antioxidant action. From the thermodynamic point of view, entering SPLET mechanism represents the most probable process in water.

Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

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Meryam Debbabi

2016-11-01

Full Text Available Lipid peroxidation products, such as 7-ketocholesterol (7KC, may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA. Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

Ascorbyl palmitate, gamma-tocopherol, and EDTA affect lipid oxidation in fish oil enriched salad dressing differently

DEFF Research Database (Denmark)

Let, M.B.; Jacobsen, Charlotte; Meyer, Anne S.

2007-01-01

The aim of the study was to investigate the ability of γ-tocopherol, ethylenediaminetetraacetate (EDTA), and ascorbyl palmitate to protect fish oil enriched salad dressing against oxidation during a 6 week storage period at room temperature. The lipid-soluble γ-tocopherol (220 and 880 µg g-1...

Tocopherol from seeds of Cucurbita pepo against diabetes: validation by in vivo experiments supported by computational docking.

Science.gov (United States)

Bharti, Sudhanshu Kumar; Kumar, Amit; Sharma, Neeraj Kumar; Prakash, Om; Jaiswal, Sudhir Kumar; Krishnan, Supriya; Gupta, Ashok Kumar; Kumar, Awanish

2013-11-01

Tocopherol from raw pumpkin seeds has been reported to be effective in the alleviation of diabetes through its antioxidant activities. This study evaluates the antidiabetic activities of the tocopherol fraction of raw seeds of Cucurbita pepo L. (CPSE) in a diabetic rat model. In addition, the putative action mechanisms of its botanicals were computationally investigated. Seed water activity (Aw) was assessed. Tocopherol was extracted and quantified from raw seed oil. The effect of CPSE was studied in poloxamer-407 (PX-407)-induced type 2 diabetic Wistar rats. Glycemic, insulinemic, and lipid profiles, as well as lipid peroxidation status, were evaluated. Glucagon like peptide-1 (GLP-1) content in the cecum was evaluated and histopathological analysis of the pancreas was performed. Further, HYBRID and FRED docking were performed for 10 documented CPSE botanicals, for putative action mechanisms concerning three proteins [protein-tyrosine phosphatase 1B (PTP-1B), peroxisome proliferator-activated receptor gamma (PPAR-γ), and dipeptidyl peptidase IV (DPP-IV)] known to have diabetic therapeutic potential. The Aw of raw seeds was found to be 0.544 ± 0.002. Using tocopherol standards, HPLC determination of CPSE revealed the presence of tocopherol isomers (α, β, γ, and δ). The tocopherol content was found to be 107.4 ± 2.9 mg/100 g of CPSE. When compared to diabetic control (DC) rats, the CPSE-treated diabetic rats presented a significant amelioration of glycemia, insulinemia, and lipid dysmetabolism. A remarkable reduction in oxidative markers and improved cecal and pancreatic characteristics were also observed. Tocopherol isomers have shown a considerable interaction potential with the aforesaid proteins in docking. The results provide pharmacological evidence of CPSE as an antihyperglycemic mediated by the interaction of various botanicals with multiple targets operating in diabetes mellitus (DM).

The influence of arachidonic acid metabolites on cell division in the intestinal epithelium and in colonic tumors.

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Petry, F M; Tutton, P J; Barkla, D H

1984-09-01

Various metabolites of arachidonic acid are now known to influence cell division. In this paper the effects on cell proliferation of arachidonic acid, some inhibitors of arachidonic acid metabolism and some analogs of arachidonic acid metabolites is described. The epithelial cell proliferation rate in the jejunum, in the descending colon and in dimethylhydrazine-induced tumors of rat colon was measured using a stathmokinetic technique. Administration of arachidonic acid resulted in retardation of cell proliferation in each of the tissues examined. A cyclooxygenase inhibitor (Flurbiprofen) prevented this effect of arachidonic acid in the jejunal crypts and in colonic tumors, but not in colonic crypts. In contrast, inhibitors of both cyclooxygenase and lipoxygenase (Benoxaprofen and BW755c) prevented the effect of arachidonic acid in the colonic crypts and reduced its effect on colonic tumours but did not alter its effect on the jejunum. An inhibitor of thromoboxane A2 synthetase (U51,605) was also able to prevent the inhibitory effect of arachidonic acid on colonic tumors. Treatment with 16,16-dimethyl PGE2 inhibited cell proliferation in jejunal crypts and in colonic tumors, as did a thromboxane A2 mimicking agent, U46619. Nafazatrom, an agent that stimulates prostacyclin synthesis and inhibits lypoxygenase, promoted cell proliferation in the jejunal crypts and colonic crypts, but inhibited cell proliferation in colonic tumours.

d-α-tocopherol nanoemulsions: Size properties, rheological behavior, surface tension, osmolarity and cytotoxicity

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M.C. Teixeira

2017-02-01

Full Text Available The aim of this study was the assessment of the physicochemical stability of d-α-tocopherol formulated in medium chain triglyceride nanoemulsions, stabilized with Tween®80 and Lipoid®S75 as surfactant and co-surfactant, respectively. d-α-tocopherol was selected as active ingredient because of its well-recognized interesting anti-oxidant properties (such as radical scavenger for food and pharmaceutical industries. A series of nanoemulsions of mean droplet size below 90 nm (polydispersity index < 0.15 have been produced by high-pressure homogenization, and their surface electrical charge (zeta potential, pH, surface tension, osmolarity, and rheological behavior, were characterized as a function of the d-α-tocopherol loading. In vitro studies in Caco-2 cell lines confirmed the safety profile of the developed nanoemulsions with percentage of cell viability above 90% for all formulations.

Oxidation of alpha-tocopherol in micelles and liposomes by the hydroxyl, perhydroxyl, and superoxide free radicals

International Nuclear Information System (INIS)

Fukuzawa, K.; Gebicki, J.M.

1983-01-01

Rates of oxidation of alpha-tocopherol by the hydroxyl- and superoxide free radicals were measured. The radicals were produced in known yields by radiolysis of aqueous solutions with gamma rays. Two main systems were used to dissolve the tocopherol; micelles, made up from charged and uncharged amphiphiles, and membranes made from dimyristyl phosphatidylcholine which could be charged by addition of stearyl amine or dicetyl phosphate. The HO. radicals were efficient oxidants of alpha-tocopherol in all systems, with up to 83% of radicals generated in micelle and 32% in membrane suspensions initiating the oxidation. The HO 2 radical was an even more effective oxidant, but when most of it was in the O 2 form at neutral or alkaline pH, the oxidation rates became low. Tocopherol held in positively charged micelles or membranes was oxidized at a higher rate by the O 2 than in uncharged or negative particles. Possible biological significance of these results is discussed

Effect of growing area on tocopherols, carotenoids and fatty acid composition of Pistacia lentiscus edible oil.

Science.gov (United States)

Mezni, F; Khouja, M L; Gregoire, S; Martine, L; Khaldi, A; Berdeaux, O

2014-01-01

In this investigation, we aim to study, for the first time, the effect of the growing area on tocopherols, carotenoids and fatty acid content of Pistacia lentiscus fixed oil. Fruits were harvested from eight different sites located in the north and the centre of Tunisia. Tocopherols, carotenoids and fatty acid content of the fixed oils were determined. The highest carotenoid content was exhibited by Feija oil (10.57 mg/kg of oil). Oueslatia and Tabarka oils displayed the highest α-tocopherol content (96.79 and 92.79 mg/kg of oil, respectively). Three major fatty acids were determined: oleic, palmitic and linoleic acids. Oleic acid was the main fatty acid presenting more than 50% of the total fatty acid content. Kebouche oil presented the highest oleic acid content (55.66%). All these results highlight the richness of carotenoids, tocopherols and unsaturated fatty acids in P. lentiscus seed oil and underscore the nutritional value of this natural product.

Plasma α-tocopherol content and its relationship with milk somatic cells count in Italian commercial herds.

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Adriano Pilotto

2015-07-01

We did not observe a correlation between plasmatic vitamin E and somatic cell score, and this can be explained by the low level of somatic cell score (averages 1.64 and 1.26. The lowest value of vitamin E was observed at parturition (1.64 µg/ml and 1.95 µg/ml. A significant (P<0.01 negative (-20% correlation was observed between NEFA serum content and α-tocopherol plasma concentration. Serum selenium content was positively correlated (+42%, P<0.0001 to zinc concentration. Grouping cows on the basis of their plasma α-tocopherol content higher or lower than 3 μg/mL at dry off, SCS at 30 and 60 DIM tended to be higher in lactating animals with lower content of α-tocopherol (1.12 vs. 1.72, P=0.18 at 30d; 0.92 vs. 1.72, P=0.07 at 60d. However, plasma α-tocopherol content at dry off could be usefully correlated with somatic cell count in fresh cows.

Atlantic Salmon (Salmo salar L. as a Marine Functional Source of Gamma-Tocopherol

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David Menoyo

2014-12-01

Full Text Available Gamma tocopherol (gT exhibits beneficial cardiovascular effects partly due to its anti-inflammatory activity. Important sources of gT are vegetable oils. However, little is known to what extent gT can be transferred into marine animal species such as Atlantic salmon by feeding. Therefore, in this study we have investigated the transfer of dietary gT into salmon. To this end, fish were fed a diet supplemented with 170 ppm gT for 16 weeks whereby alpha tocopherol levels were adjusted to 190 ppm in this and the control diet. Feeding gT-rich diets resulted in a three-fold increase in gT concentrations in the liver and fillet compared to non-gT-supplemented controls. Tissue alpha tocopherol levels were not decreased indicating no antagonistic interaction between gamma- and alpha tocopherol in salmon. The concentration of total omega 3 fatty acids slightly increased in response to dietary gT. Furthermore, dietary gT significantly decreased malondialdehyde in the fillet, determined as a biomarker of lipid peroxidation. In the liver of gT fed salmon we observed an overall down-regulation of genes involved in lipid homeostasis. Additionally, gT improved the antioxidant capacity by up-regulating Gpx4a gene expression in the pyloric caeca. We suggest that Atlantic salmon may provide a marine functional source capable of enriching gT for human consumption.

Study of alpha-tocopherol as a protector of damages induced to the skin by ionizing radiation

International Nuclear Information System (INIS)

Lucero, M.J.; Vigo, J.; Leon, M.J.; Sanchez, J.A.; Martin, F.

1997-01-01

An experimental study was carried out in animals for determining the characteristics of alpha-tocopherol protection against lesions caused by free radicals produced by ionizing radiation. Two different concentrations of alpha-tocopherol were applied on the same exposed sample. A linear electron accelerator of 6 MeV was used for the production of free radicals and a dose of 2800 cGy. The lesions were submitted to clinical studies for anatomic pathologies. The conclusion of this study is that alpha-tocopherol applied to skin before and immediately after the exposure to ionizing radiation has the capability to protect it, developing a perfectly differentiated epidermis and of greater thickness than normally considered

Effects of dietary [alpha]-tocopherol and [beta]-carotene on lipid peroxidation induced by methyl mercuric chloride in mice

Energy Technology Data Exchange (ETDEWEB)

Raun Andersen, H; Andersen, O [Department of Environmental Medicine, University of Odense, Odense (Denmark)

1993-01-01

Exposure of male CBA mice to methyl mercuric chloride, CH[sub 3]HgCl, (10-40 mg/l in drinking water) for 2 weeks resulted in dose-related Hg deposition and enhanced lipid peroxidation in liver, kidney and brain. Mice were fed well-defined semisynthetic diets containing different levels of [alpha]-tocopherol (10, 100 or 1000 mg/kg) or [beta]-carotene (1000, 10,000 or 100,000 IU/kg) for four weeks, two groups on each diet. The concentration of [alpha]-tocopherol and [beta]-carotene used corresponded to deficient, normal and high levels. During the last two weeks, one group on each diet was given 40 mg CH[sub 3]HgCl/l of drinking water. High dietary [alpha]-tocopherol protected against CH[sub 3]HgCl induced hepatic lipid peroxidation, whereas the [alpha]-tocopherol deficient diet further enhanced CH[sub 3]HgCl induced hepatic lipid peroxidation. Similar, though statistically non-significant effects occurred in the kidneys, [alpha]-tocopherol did not protect against CH[sub 3]HgCl induced lipid peroxidation in the brain. Excess dietary [beta]-carotene further enhanced CH[sub 3]HgCl induced lipid peroxidation in liver, kidney and brain. CH[sub 3]HgCl significantly decreased the activity of total glutathione peroxidase (T-GSH-Px) and Se-dependent glutathione peroxidase (Se-GSH-Px) in the kidneys in all dietary groups. High dietary [alpha]-tocopherol enhanced the activity of Se-GSH-Px in liver and kidney compared to the activity in mice fed the normal level of [alpha]-tocopherol. This occurred in mice exposed to CH[sub 3]-HgCl as well as in unexposed mice, and the difference between CH[sub 3]HgCl exposed and unexposed mice was not diminished. High dietary [alpha]-tocopherol increased the activity of both Se-GSH-Px and T-GSH-Px in the brain of CH[sub 3]HgCl-exposed mice. The dietary level of [beta]-carotene did not affect the activity of the two enzymes in the organs investigated. (au) (43 refs.).

Effects of dietary α-tocopherol and β-carotene on lipid peroxidation induced by methyl mercuric chloride in mice

International Nuclear Information System (INIS)

Raun Andersen, H.; Andersen, O.

1993-01-01

Exposure of male CBA mice to methyl mercuric chloride, CH 3 HgCl, (10-40 mg/l in drinking water) for 2 weeks resulted in dose-related Hg deposition and enhanced lipid peroxidation in liver, kidney and brain. Mice were fed well-defined semisynthetic diets containing different levels of α-tocopherol (10, 100 or 1000 mg/kg) or β-carotene (1000, 10,000 or 100,000 IU/kg) for four weeks, two groups on each diet. The concentration of α-tocopherol and β-carotene used corresponded to deficient, normal and high levels. During the last two weeks, one group on each diet was given 40 mg CH 3 HgCl/l of drinking water. High dietary α-tocopherol protected against CH 3 HgCl induced hepatic lipid peroxidation, whereas the α-tocopherol deficient diet further enhanced CH 3 HgCl induced hepatic lipid peroxidation. Similar, though statistically non-significant effects occurred in the kidneys, α-tocopherol did not protect against CH 3 HgCl induced lipid peroxidation in the brain. Excess dietary β-carotene further enhanced CH 3 HgCl induced lipid peroxidation in liver, kidney and brain. CH 3 HgCl significantly decreased the activity of total glutathione peroxidase (T-GSH-Px) and Se-dependent glutathione peroxidase (Se-GSH-Px) in the kidneys in all dietary groups. High dietary α-tocopherol enhanced the activity of Se-GSH-Px in liver and kidney compared to the activity in mice fed the normal level of α-tocopherol. This occurred in mice exposed to CH 3 -HgCl as well as in unexposed mice, and the difference between CH 3 HgCl exposed and unexposed mice was not diminished. High dietary α-tocopherol increased the activity of both Se-GSH-Px and T-GSH-Px in the brain of CH 3 HgCl-exposed mice. The dietary level of β-carotene did not affect the activity of the two enzymes in the organs investigated. (au) (43 refs.)

Effect of hydroxyapatite particle size, morphology and crystallinity on proliferation of colon cancer HCT116 cells

Energy Technology Data Exchange (ETDEWEB)

Dey, Sangeeta; Das, Mitun, E-mail: mitun@cgcri.res.in; Balla, Vamsi Krishna

2014-06-01

The aim of the present work is to chemically and physically characterize the synthesized Hydroxyapatite (HAp) micro and nanoparticles and to explore the inhibitory effect of nano-HAps on the in vitro growth of human colon cancerous cells HCT116. HAp powder was synthesized using three different routes to achieve micro and nanosized powders, with different morphologies and crystallinity. The synthesized powders were characterized using X-ray diffraction, FTIR spectroscopy and scanning electron microscope. The results showed that the average crystallite size of HAp powder varies from 11 nm to 177 nm and respective crystallinity of powder found to be in the range of 0.12 and 0.92. The effect of these physico-chemical properties of HAp powders on human colon cancer HCT116 cells inhibition was determined in vitro. It was found that decreasing the HAp powder crystallite size between 11 nm and 22 nm significantly increases the HCT116 cell inhibition. Our results demonstrate that apart from HAp powder size their crystallinity and morphology also play an important role in cellular inhibition of human colon cancer cells. - Highlights: • Chemically synthesized hydroxyapatite micro and nano-particles with different morphologies and crystallinity. • In vitro cell–material interaction showed that hydroxyapatite nano-particles inhibit colon cancer cells. • Human colon cancer cell inhibition also depends on crystallinity and morphology of HAp powder.

Tocopherols and phytosterols in sunflower seeds for the human food market

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Fernández-Cuesta, A.

2012-09-01

Full Text Available Sunflower seeds for the human food market are derived from both oilseed-type cultivars, with black achenes and low hull proportion, and confectionery-type cultivars, with striped achenes and high hull proportion. The objective of this research was to evaluate tocopherol and phytosterol contents in the seeds of both types of cultivars. Five oilseed-type and seven confectionery-type cultivars were evaluated in replicated field trials in two locations of Morocco and Spain. Large variations were found in hundred-kernel weight (2.6 to 5.5 g, kernel oil content (42.7 to 67.5%, tocopherol content (203 to 397 mg kg^–1 kernel, and phytosterol content (2179 to 3555 mg kg^–1 kernel. Both types of cultivars did not differ for kernel weight, kernel oil content, or tocopherol and phytosterol profiles. However, oilseed-type cultivars had significantly greater average tocopherol and phytosterol contents, though confectionery-type cultivars with levels of tocopherols and phytosterols similar to the best oilseed-type cultivars were identified. The large variations in kernel tocopherol and phytosterol contents found in this research suggest that there is room for breeding for increased levels of these compounds in order to develop healthier sunflower cultivars for the human food market.

Las semillas de girasol para consumo directo proceden tanto de cultivares oleaginosos, con aquenios negros y baja proporción de cáscara, como de cultivares de consumo directo, con aquenios de colores claros o rayados y elevada proporción de cáscara. El objetivo de este trabajo fue evaluar el contenido en tocoferoles y fitoesteroles en semillas de ambos tipos de cultivares. Se evaluaron cinco cultivares oleaginosos y siete cultivares de consumo directo en ensayos de campo replicados en dos localidades de Marruecos y España. Se identificó gran variación para peso de 100 semillas (aquenios descascarillados; 2.6 a 5.5 g, contenido en aceite en la

Distribution of Tocopherols and Tocotrienols in Guinea Pig Tissues Following Parenteral Lipid Emulsion Infusion.

Science.gov (United States)

Xu, Zhidong; Harvey, Kevin A; Pavlina, Thomas M; Zaloga, Gary P; Siddiqui, Rafat A

2016-07-01

Tocopherols and tocotrienols possess vitamin E activity and function as the major lipid-soluble antioxidants in the human body. Commercial lipid emulsions are composed of different oils and supply different amounts of vitamin E. The objective of this study was to measure all 8 vitamin E homologs within 4 different commercial lipid emulsions and evaluate their distribution in guinea pig tissues. The distribution of vitamin E homologs within plasma and guinea pig tissues was determined using a high-performance liquid chromatography (HPLC) system. Lipid hydroperoxides in lipid emulsions were determined using a commercial kit (Cayman Chemical Company, Ann Arbor, MI), and malondialdehyde tissue levels were determined using an HPLC system. The lipid emulsions contained variable amounts of tocopherols, which were significantly different between emulsions. Tocotrienols were present at very low concentrations (≤0.3%). We found no correlation between the amount of vitamin E present in the lipid emulsions and lipid peroxidation. Hydroperoxides were the lowest with an olive oil-based emulsion and highest with a fish oil emulsion. The predominant vitamin E homolog in guinea pig tissues was α-tocopherol. No tissues had detectable levels of tocotrienols. Vitamin E levels (primarily α-tocopherol and γ-tocopherol) were highly variable among organ tissues. Plasma levels were a poor reflection of most tissue levels. Vitamin E levels within different lipid emulsions and plasma/tissues are highly variable, and no one tissue or plasma sample serves as a good proxy for levels in other tissues. All study emulsions were well tolerated and did not significantly increase systemic lipid peroxidation. © 2014 American Society for Parenteral and Enteral Nutrition.

Members of native coral microbiota inhibit glycosidases and thwart colonization of coral mucus by an opportunistic pathogen.

Science.gov (United States)

Krediet, Cory J; Ritchie, Kim B; Alagely, Ali; Teplitski, Max

2013-05-01

The outcome of the interactions between native commensal microorganisms and opportunistic pathogens is crucial to the health of the coral holobiont. During the establishment within the coral surface mucus layer, opportunistic pathogens, including a white pox pathogen Serratia marcescens PDL100, compete with native bacteria for available nutrients. Both commensals and pathogens employ glycosidases and N-acetyl-glucosaminidase to utilize components of coral mucus. This study tested the hypothesis that specific glycosidases were critical for the growth of S. marcescens on mucus and that their inhibition by native coral microbiota reduces fitness of the pathogen. Consistent with this hypothesis, a S. marcescens transposon mutant with reduced glycosidase and N-acetyl-glucosaminidase activities was unable to compete with the wild type on the mucus of the host coral Acropora palmata, although it was at least as competitive as the wild type on a minimal medium with glycerol and casamino acids. Virulence of the mutant was modestly reduced in the Aiptasia model. A survey revealed that ∼8% of culturable coral commensal bacteria have the ability to inhibit glycosidases in the pathogen. A small molecular weight, ethanol-soluble substance(s) produced by the coral commensal Exiguobacterium sp. was capable of the inhibition of the induction of catabolic enzymes in S. marcescens. This inhibition was in part responsible for the 10-100-fold reduction in the ability of the pathogen to grow on coral mucus. These results provide insight into potential mechanisms of commensal interference with early colonization and infection behaviors in opportunistic pathogens and highlight an important function for the native microbiota in coral health.

Hath1 inhibits proliferation of colon cancer cells probably through up-regulating expression of Muc2 and p27 and down-regulating expression of cyclin D1.

Science.gov (United States)

Zhu, Dai-Hua; Niu, Bai-Lin; Du, Hui-Min; Ren, Ke; Sun, Jian-Ming; Gong, Jian-Ping

2012-01-01

Previous studies showed that Math1 homologous to human Hath1 can cause mouse goblet cells to differentiate. In this context it is important that the majority of colon cancers have few goblet cells. In the present study, the potential role of Hath1 in colon carcinogenesis was investigated. Sections of paraffin-embedded tissues were used to investigate the goblet cell population of normal colon mucosa, mucosa adjacent colon cancer and colon cancer samples from 48 patients. Hath1 and Muc2 expression in these samples were tested by immunohistochemistry, quantitative real-time reverse transcription -PCR and Western blotting. After the recombinant plasmid, pcDNA3.1(+)-Hath1 had been transfected into HT29 colon cancer cells, three clones were selected randomly to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time reverse transcription-PCR and Western blotting. Moreover, the proliferative ability of HT29 cells introduced with Hath1 was assessed by means of colony formation assay and xenografting. Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected by Western blotting. No goblet cells were to be found in colon cancer and levels of Hath1 mRNA and Hath1, Muc2 mRNA and Muc2 were significantly down-regulated. Hath1 could decrease cyclin D1, increase p27 and Muc2 in HT29 cells and inhibit their proliferation. Hath1 may be an anti-oncogene in colon carcinogenesis.

Tocopherol And Tocotrienol: Therapeutic Potential In Animal Models of Stress.

Science.gov (United States)

Azlina, Mohd Fahami Nur; Kamisah, Yusof; Qodriyah, Mohd Saad

2017-11-22

Scientific reports had shown that stress is related to numerous pathological changes in the body. These pathological changes can bring about numerous diseases and can significantly cause negative effects in an individual. These include gastric ulcer, liver pathology and neurobehavioral changes. A common pathogenesis in many diseases related to stress involves oxidative damage. Therefore, the administration of antioxidants such as vitamin E is a reasonable therapeutic approach. However, there is conflicting evidence about antioxidant supplementation. The aim of this work was to summarize documented reports on the effects of tocopherol and tocotrienol on various pathological changes induced by stress. This review will reveal the scientific evidence of enteral supplementation of vitamin E in the forms of tocotrienol and tocopherol in animal models of stress. These models mimic the stress endured by critically ill patients in a clinical setting and psychological stress in individuals. Positive outcomes from enteral feeding of vitamin E in reducing the occurrence of stress-induced pathological changes are discussed in this review. These positive findings include their ability to reduced stress-induced gastric ulcers, elevated liver enzymes and improved locomotors activity. Evidences showing tocotrienol and tocopherol effects are not just related to its ability to reduce oxidative stress but also acting on other mechanism are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Physico-chemical properties, fatty acid and tocopherol composition of oils from some Sudanese oil bearing sources

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Matthäus, Bertrand

2008-12-01

Full Text Available Seven oils, obtained from seven Sudanese oil bearing sources that are Albizia lebbek Oil (ALO, Cassia obtusifolia Oil (COO, Cassia occidentalis Oil (CCO, Abutilon pannosum Oil (APO, Mitracarpus villous Oil (MVO, Ipomea indica Oil (IIO and Sesamum alatum Oil (SAO, were investigated. The seeds were collected in Sudan from Ghibaish, North Kordofan state. In addition to the oil content, the fatty acid was determined by capillary gas chromatography and the tocopherols were evaluated by highperformance liquid chromatography. The oil content of the seven seeds amounted to 12.8, 7.0, 3.2, 7.1, 11.5, 8.8, and 21.3%, respectively.The oils contained 16.4, 20.0, 14.3, 16.8, 19.4, 19.9 and 10.9 % palmitic acid and 21.0, 24.4, 22.1, 10.9, 27.7, 34.0, 45.1 % oleic acid, and 43.8, 38.2, 45.0, 63.9, 34.6, 33.5, 36.3 % linoleic acid and traces of linolenic acid, respectively.The tocopherol content of these oils amounted to 85.6, 48.2, 32.7, 163.5, 52.5, 30.9, and 26.4 mg/100 g oil, respectively. Alpha-tocopherol was the predominant tocopherol in the oil of Albizia lebbek, Cassia obtusifolia, Cassia occidentalis, and Abutilon pannosum, while gamma-tocopherol was the predominant tocopherol in the oil of Mitracarpus villous, Ipomea indica and Sesamum alatum.Se analizan siete aceites procedentes de plantas y semillas de Sudán: Albizia lebbek Oil (ALO, Cassia obtusifolia Oil (COO, Cassia occidentalis Oil (CCO, Abutilon pannosum Oil (APO, Mitracarpus villous Oil (MVO, Ipomea indica Oil (IIO y Sesamum alatum Oil (SAO. Las semillas se recolectaron en el estado de Ghibaish, North Kordofan. Además del contenido en aceite (12.8, 7.0, 3.2, 7.1, 11.5, 8.8, y 21.3 %, respectivamente, se determinaron los ácidos grasos mediante cromatografía de gases y los tocoferoles mediante HPLC. Los aceites contenían, respectivamente, 16.4, 20.0, 14.3, 16.8, 19.4, 19.9 y 10.9 % de ácido palmitito, 21.0, 24.4, 22.1, 10.9, 27.7, 34.0, 45.1 % de ácido oleico, 43.8, 38.2, 45.0, 63.9, 34

Influence of fasting on circulating levels of alpha-tocopherol and beta-carotene. Effect of short-term supplementation

NARCIS (Netherlands)

Brouwer, DAJ; Molin, F; van Beusekom, CM; van Doormaal, JJ; Muskiet, FAJ

1998-01-01

We investigated the influence of fasting on the levels of alpha-tocopherol in plasma, erythrocytes and platelets, and on plasma beta-carotene. Six apparently healthy adults were subjected to 17-h feed-fasting experiments at various days before, during and after supplementation with alpha-tocopherol

STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH+/CD133+ stem cell-like human colon cancer cells

International Nuclear Information System (INIS)

Lin, Li; Fuchs, James; Li, Chenglong; Olson, Veronica; Bekaii-Saab, Tanios; Lin, Jiayuh

2011-01-01

Highlights: ► The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. ► STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. ► Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. ► STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. ► Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH + /CD133 + ). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower IC50 in colon cancer stem-like cells. In summary, our results indicate that STAT3 is a novel therapeutic target in colon cancer stem

Distribution of vitamins A (retinol) and E (alpha-tocopherol) in polar bear kidney: Implications for biomarker studies

DEFF Research Database (Denmark)

Bechshøft, T.Ø.; Jakobsen, Jette; Sonne, C.

2011-01-01

of the organ to sample in order to get a representative value for this important biomarker. The aim here was to assess the distribution of vitamins A (retinol) and E (α-tocopherol) within the polar bear multireniculate kidney (i.e. polar vs. medial position) and also within the cortex vs. medulla of each...... separate renculi. The results showed no significant difference between the medial and polar renculi with regards to either retinol (p=0.44) or α-tocopherol (p=0.75). There were, however, significant differences between cortex and medulla for both vitamins (retinol, p=0.0003; α-tocopherol, p...

Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells

Directory of Open Access Journals (Sweden)

Park Hae-Duck

2011-07-01

Full Text Available Abstract Background Polysaccharides extracted from the Phellinus linteus (PL mushroom are known to possess anti-tumor effects. However, the molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Experiments were carried out to unravel the anticancer effects of PL. Methods The anti-cancer effects of PL were examined in SW480 colon cancer cells by evaluating cell proliferation, invasion and matrix metallo-proteinase (MMP activity. The anti-angiogenic effects of PL were examined by assessing human umbilical vein endothelial cell (HUVEC proliferation and capillary tube formation. The in vivo effect of PL was evaluated in an athymic nude mouse SW480 tumor engraft model. Results PL (125-1000 μg/mL significantly inhibited cell proliferation and decreased β-catenin expression in SW480 cells. Expression of cyclin D1, one of the downstream-regulated genes of β-catenin, and T-cell factor/lymphocyte enhancer binding factor (TCF/LEF transcription activity were also significantly reduced by PL treatment. PL inhibited in vitro invasion and motility as well as the activity of MMP-9. In addition, PL treatment inhibited HUVEC proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice was significantly decreased as a consequence of PL treatment, and tumor tissues from treated animals showed an increase in the apoptotic index and a decrease in β-catenin expression. Moreover, the proliferation index and microvessel density were significantly decreased. Conclusions These data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/β-catenin signaling in certain colon cancer cells.

Influence of Alpha Tocopherol on Heat Stress-Induced Changes in the Reproductive Function of Swiss Albino Mice

International Nuclear Information System (INIS)

AlEnazi, Maher M.

2007-01-01

The present study was carried out to investigate the influence of vitamin E (alpha-tocopherol) on heat stress-induced changes in the reproduction of Swiss albino mice. The evaluated parameters include: the estrous cycle, fertility, post-implantation losses of fetuses and estimation of progesterone levels in the serum. Eight groups of experimental mice (10 each) were used. Groups 1-4 (24 degree C) consisted of a control and alpha-tocopherol (100, 200 and 400 mg/kg) treated groups. Groups 5-8 (42 degree C) consisted of a positive control and alpha-tocopherol (100, 200 and 400 mg/kg) treated group. Heat-stress reduced significantly (p > 0.001) the number of fetuses and corpora lutea. There was also a significant decrease in the mean weights of fetuses (p > 0.001) and placenta (p > 0.01) in the heat-stress group with a decrease in their serum progesterone levels (p > 0.01). Heat-stress groups treated with high doses of alpha-tocopherol 200 and 400 mg/kg, showed protection against heat-stress related abnormalities. The results showed that alpha-tocopherol plays a role in protection against hyperthermia induced changes in the estrous cycle length, infertility, post-implantation losses and depletion in the serum level of progesterone. (author)

A pharmacological analysis elucidating why, in contrast to (-)-deprenyl (selegiline), alpha-tocopherol was ineffective in the DATATOP study.

Science.gov (United States)

Miklya, I; Knoll, B; Knoll, J

2003-04-25

The Parkinson Study Group who conducted the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial designed their study in the belief that the MAO inhibitor (-)-deprenyl (selegiline), the antioxidant alpha-tocopherol, and the combination of the two compounds will slow the clinical progression of the disease to the extent that MAO activity and the formation of oxygen radicals contribute to the pathogenesis of nigral degeneration. In fact, (-)-deprenyl only delayed the onset of disability associated with early, otherwise untreated Parkinson's disease, however, in contrast to the expectation of the authors, alpha-tocopherol proved to be ineffective in the DATATOP study. Enhancer substances, (-)-deprenyl, (-)-1-phenyl-2-propylaminopentane [(-)-PPAP] the (-)-deprenyl analogue free of MAO inhibitory potency, and R-(-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] the presently known most potent enhancer substance, are peculiar stimulants. They enhance the impulse propagation mediated release of the catecholamines in the brain. Due to their enhancer effect, the amount of catecholamines released from selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus) is significantly higher in rats treated with an enhancer substance than in saline treated rats. We compared the effect of (-)-deprenyl 0.025 and 0.25 mg/kg, (-)-PPAP 0.1 mg/kg, (-)-BPAP 0.0001 mg/kg, and alpha-tocopherol 25 and 50 mg/kg, in this test. The doses of (-)-deprenyl and alpha-tocopherol were selected to be in compliance with the dose given in the DATATOP study. Compared to saline treated rats, the enhancer substances significantly increased the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium and the amount of norepinephrine released from the locus coeruleus; alpha-tocopherol was ineffective. The results indicate that alpha-tocopherol was ineffective, because, unlike (-)-deprenyl it dose not enhance

Increased sensitivity to salt stress in tocopherol-deficient Arabidopsis mutants growing in a hydroponic system

Science.gov (United States)

Ellouzi, Hasna; Hamed, Karim Ben; Cela, Jana; Müller, Maren; Abdelly, Chedly; Munné-Bosch, Sergi

2013-01-01

Recent studies suggest that tocopherols could play physiological roles in salt tolerance but the mechanisms are still unknown. In this study, we analyzed changes in growth, mineral and oxidative status in vte1 and vte4 Arabidopsis thaliana mutants exposed to salt stress. vte1 and vte4 mutants lack α-tocopherol, but only the vte1 mutant is additionally deficient in γ-tocopherol. Results showed that a deficiency in vitamin E leads to reduced growth and increased oxidative stress in hydroponically-grown plants. This effect was observed at early stages, not only in rosettes but also in roots. The vte1 mutant was more sensitive to salt-induced oxidative stress than the wild type and the vte4 mutant. Salt sensitivity was associated with (i) high contents of Na+, (ii) reduced efficiency of PSII photochemistry (Fv/Fm ratio) and (iii) more pronounced oxidative stress as indicated by increased hydrogen peroxide and malondialdeyde levels. The vte 4 mutant, which accumulates γ- instead of α-tocopherol showed an intermediate sensitivity to salt stress between the wild type and the vte1 mutant. Contents of abscisic acid, jasmonic acid and the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid were higher in the vte1 mutant than the vte4 mutant and wild type. It is concluded that vitamin E-deficient plants show an increased sensitivity to salt stress both in rosettes and roots, therefore indicating the positive role of tocopherols in stress tolerance, not only by minimizing oxidative stress, but also controlling Na+/K+ homeostasis and hormonal balance. PMID:23299430

Effect of astaxanthin in combination with alpha-tocopherol or ascorbic acid against oxidative damage in diabetic ODS rats.

Science.gov (United States)

Nakano, Masako; Onodera, Aya; Saito, Emi; Tanabe, Miyako; Yajima, Kazue; Takahashi, Jiro; Nguyen, Van Chuyen

2008-08-01

The present study was performed to investigate the effect of astaxanthin in combination with other antioxidants against oxidative damage in streptozotocin (STZ)-induced diabetic Osteogenic Disorder Shionogi (ODS) rats. Diabetic-ODS rats were divided into five groups: control, astaxanthin, ascorbic acid, alpha-tocopherol, and tocotrienol. Each of the four experimental groups was administered a diet containing astaxanthin (0.1 g/kg), in combination with ascorbic acid (3.0 g/kg), alpha-tocopherol (0.1 g/kg), or tocotrienol (0.1 g/kg) for 20 wk. The effects of astaxanthin with other antioxidants on lipid peroxidation, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) excretion, serum creatinine (Cr) level, creatinine clearance (Ccr), and urinary protein content were assessed. The serum lipid peroxide levels and chemiluminescent (CL) intensity in the liver of the alpha-tocopherol and tocotrienol groups were significantly reduced in comparison to that of the control group. In the alpha-tocopherol group, urinary 8-OHdG excretion, serum Cr level, Ccr, urinary albumin excretion, and urinary protein concentration were significantly decreased as compared with those in the control group. Additionally, the CL intensity in the kidney of the alpha-tocopherol group was significantly lower, but that of the ascorbic acid group was significantly higher than that in the control group. These results indicate that dietary astaxanthin in combination with alpha-tocopherol has an inhibitory effect on oxidative stress. On the other hand, our study suggests that excessive ascorbic acid intake increases lipid peroxidation in diabetic rats.

Tocopherol and tocotrienol contents of different varieties of rice in Malaysia.

Science.gov (United States)

Shammugasamy, Balakrishnan; Ramakrishnan, Yogeshini; Ghazali, Hasanah M; Muhammad, Kharidah

2015-03-15

The present study examined the contents of tocopherols and tocotrienols and their distribution in 58 different varieties of whole rice cultivated in Malaysia. The analytical method used was saponification of samples followed by dispersive liquid-liquid microextraction and reverse phase high-performance liquid chromatography. The total vitamin E contents of different varieties of whole rice ranged between 19.36 and 63.29 mg kg⁻¹. Contents of vitamin E isomers varied among rice varieties both within and between grain color groups. Black-pigmented rice showed significantly higher mean contents of α-tocopherol, β-tocopherol and α-tocotrienol than non-pigmented rice and red-pigmented rice. Red-pigmented rice had significantly lower mean contents of γ-tocotrienol and total vitamin E than non-pigmented rice. The mean contents of δ-tocotrienol and total vitamin E in non-pigmented rice, however, were similar to those in black-pigmented rice. γ-Tocotrienol was the predominant form of vitamin E isomer in all analyzed varieties. The Pearson correlations among vitamin E isomers and total vitamin E content of whole rice were also studied. This study provides information on vitamin E content of different rice varieties that would be beneficial for decision making in genetic breeding of bioactive compound-rich rice varieties. © 2014 Society of Chemical Industry.

Overexpression of Long Non-Coding RNA TUG1 Promotes Colon Cancer Progression.

Science.gov (United States)

Zhai, Hui-Yuan; Sui, Ming-Hua; Yu, Xiao; Qu, Zhen; Hu, Jin-Chen; Sun, Hai-Qing; Zheng, Hai-Tao; Zhou, Kai; Jiang, Li-Xin

2016-09-16

BACKGROUND Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. MATERIAL AND METHODS qRT-PCR was used to analyze the expression level of TUG1 and p63 in 75 colon cancer tissues and the matched adjacent non-tumor tissue. In vitro, cultured colon cancer cell lines HCT-116 and LoVo were used as cell models. TUG1 and p63 were silenced via transferring siRNA into HCT-116 or LoVo. The effects of TUG1 were investigated by examining cell proliferation, apoptosis, and migration. RESULTS Among the 75 colon cancer cases, the expression of TUG1 was significantly higher in colon cancer tissues compared with the matched adjacent non-tumor tissue, while p63 expression was lower in the tumor tissue. In HCT-116 and LoVo, the expression of TUG1 was significantly increased by p63 siRNA transfection. Furthermore, down-regulation of TUG1 by siRNA significantly inhibited the cell proliferation and promoted colon cancer cell apoptosis. In addition, inhibition of TUG1 expression significantly blocked the cell migration ability of colon cancer cells. CONCLUSIONS LncRNA TUG1 may serve as a potential oncogene for colon cancer. Overexpressed TUG1 may contribute to promoting cell proliferation and migration in colon cancer cells.

Dietary, Supplement, and Adipose Tissue Tocopherols Levels in Relation to Prostate Cancer Aggressiveness Among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP)

Science.gov (United States)

Antwi, Samuel; Steck, Susan E.; Su, L. Joseph; Hebert, James R.; Zhang, Hongmei; Fontham, Elizabeth T. H.; Smith, Gary; Bensen, Jeannette T.; Mohler, James L.; Arab, Lenore

2016-01-01

Background Controversies remain over the safety and efficacy of vitamin E (i.e., α–tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. Methods This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n=1,023) and European-American (EA, n=1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated from logistic regression comparing high aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. Results Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95% CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17–0.69), Ptrend = 0.006; δ-tocopherol, 0.45 (0.21–0.95) Ptrend = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95% CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28–1.19), Ptrend = 0.20; supplemental α-tocopherol, 0.64 (0.31–1.21) Ptrend = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95% CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66–3.11) and AAs 0.66 (0.27–1.62)]. Conclusions The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. PMID:26053590

Dietary, supplement, and adipose tissue tocopherol levels in relation to prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP).

Science.gov (United States)

Antwi, Samuel O; Steck, Susan E; Su, L Joseph; Hébert, James R; Zhang, Hongmei; Fontham, Elizabeth T H; Smith, Gary J; Bensen, Jeannette T; Mohler, James L; Arab, Lenore

2015-09-01

Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17-0.69), P(trend)  = 0.006; δ-tocopherol, 0.45 (0.21-0.95) P(trend)  = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28-1.19), P(trend)  = 0.20; supplemental α-tocopherol, 0.64 (0.31-1.21) P(trend)  = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66-3.11) and AAs 0.66 (0.27-1.62)]. The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. © 2015 Wiley Periodicals, Inc.

Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

International Nuclear Information System (INIS)

Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang; Dong, Wei-Guo

2012-01-01

Highlights: ► Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. ► G 2 /M phase arrest and chromatin condensation and nuclear fragmentation were induced. ► Noscapine promoted apoptosis via mitochondrial pathways. ► Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC 50 = 75 μM). This cytotoxicity was reflected by cell cycle arrest at G 2 /M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

Biodegradable films containing {alpha}-tocopherol/{beta}-cyclodextrin complex; Filmes biodegradaveis contendo {alpha}-tocoferol complexado em {beta}-ciclodextrina

Energy Technology Data Exchange (ETDEWEB)

Motta, Caroline; Martelli, Silvia M.; Soldi, Valdir, E-mail: vsoldi@qmc.ufsc.br [Lab. de Materiais Polimericos (POLIMAT), Dept. de Quimica, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Barreto, Pedro L.M. [Lab. de Reologia (REOLAB), Dept. de Ciencia e Tecnologia de Alimentos, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil)

2011-07-01

The growing environmental concern about pollution and the need to reduce dependence of plastic industry in relation to non-renewable resources has increased the interest of both researchers and industry in the use of biopolymers. In this work {beta}-cyclodextrin/{alpha}-tocopherol complexes were prepared and characterized. In order to obtain polymeric active biofilms, the {beta}-cyclodextrin/{alpha}-tocopherol complex was incorporated into a polymeric matrix of carboxymethylcellulose. The {beta}-cyclodextrin/{alpha}-tocopherol complex was characterized through of X-ray diffraction and thermogravimetric analysis. The physicochemical properties of the films incorporated with the complex were evaluated through mechanical and colorimetric analysis and moisture sorption isotherm. (author)

Malignant transformation of colonic epithelial cells by a colon-derived long noncoding RNA

International Nuclear Information System (INIS)

Franklin, Jeffrey L.; Rankin, Carl R.; Levy, Shawn; Snoddy, Jay R.; Zhang, Bing; Washington, Mary Kay; Thomson, J. Michael; Whitehead, Robert H.; Coffey, Robert J.

2013-01-01

Highlights: •Non-coding RNAs are found in the colonic crypt progenitor compartment. •Colonocytes transformed by ncNRFR are highly invasive and metastatic. •ncNRFR has a region similar to the miRNA, let-7 family. •ncNRFR expression alters let-7 activity as measured by reporter construct. •ncNRFR expression upregulates let-7b targets. -- Abstract: Recent progress has been made in the identification of protein-coding genes and miRNAs that are expressed in and alter the behavior of colonic epithelia. However, the role of long non-coding RNAs (lncRNAs) in colonic homeostasis is just beginning to be explored. By gene expression profiling of post-mitotic, differentiated tops and proliferative, progenitor-compartment bottoms of microdissected adult mouse colonic crypts, we identified several lncRNAs more highly expressed in crypt bottoms. One identified lncRNA, designated non-coding Nras functional RNA (ncNRFR), resides within the Nras locus but appears to be independent of the Nras coding transcript. Stable overexpression of ncNRFR in non-transformed, conditionally immortalized mouse colonocytes results in malignant transformation, as determined by growth in soft agar and formation of highly invasive tumors in nude mice. Moreover, ncNRFR appears to inhibit the function of the tumor suppressor let-7. These results suggest precise regulation of ncNRFR is necessary for proper cell growth in the colonic crypt, and its misregulation results in neoplastic transformation

Simultaneous analysis of carotenoids and tocopherols in botanical species using one step solid-liquid extraction followed by high performance liquid chromatography.

Science.gov (United States)

Valdivielso, Izaskun; Bustamante, María Ángeles; Ruiz de Gordoa, Juan Carlos; Nájera, Ana Isabel; de Renobales, Mertxe; Barron, Luis Javier R

2015-04-15

Carotenoids and tocopherols from botanical species abundant in Atlantic mountain grasslands were simultaneously extracted using one-step solid-liquid phase. A single n-hexane/2-propanol extract containing both types of compounds was injected twice under two different sets of HPLC conditions to separate the tocopherols by normal-phase chromatography and carotenoids by reverse-phase mode. The method allowed reproducible quantification in plant samples of very low amounts of α-, β-, γ- and δ-tocopherols (LOD from 0.0379 to 0.0720 μg g(-1) DM) and over 15 different xanthophylls and carotene isomers. The simplified one-step extraction without saponification significantly increased the recovery of tocopherols and carotenoids, thereby enabling the determination of α-tocopherol acetate in plant samples. The two different sets of chromatographic analysis provided near baseline separation of individual compounds without interference from other lipid compounds extracted from plants, and a very sensitive and accurate detection of tocopherols and carotenoids. The detection of minor individual components in botanical species from grasslands is nowadays of high interest in searching for biomarkers for foods derived from grazing animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Methyl jasmonate differentially affects tocopherol content and tyrosine amino transferase activity in cultured cells of Amaranthus caudatus and Chenopodium quinoa.

Science.gov (United States)

Antognoni, F; Faudale, M; Poli, F; Biondi, S

2009-03-01

Tocopherols are lipid-soluble compounds synthesised exclusively by photosynthetic organisms. In this study, in vitro callus cultures were established from two plants that are naturally rich in tocopherols, Amaranthus caudatus and Chenopodium quinoa, in order to examine whether callus cultures were able to produce these compounds at levels comparable to those observed in planta. In both species, cotyledon explants produced the best callus induction and, once established, callus cultures were grown under two different hormonal treatments to check for effects of growth and to induce chloroplast differentiation in the cells. A rapid differentiation of chloroplasts occurred only in C. quinoa cell aggregates grown in the presence of benzyladenine, leading to the production of a homogeneous green callus. In both species, only alpha-tocopherol was produced by callus cultures, although levels were much lower than in planta, and the production was not influenced by the hormonal conditions. Interestingly, cell cultures of the two species responded in different ways to methyl jasmonate (MJ). In A. caudatus cultures, treatment with 100 mum MJ increased the production of alpha-tocopherol up to fivefold, and the inductive effect was influenced by the hormonal composition of the medium. This increase in alpha-tocopherol was associated with a proportional increase in tyrosine aminotransferase (TAT) activity, one of the key enzymes involved in tocopherol biosynthesis. By contrast, in C. quinoa cultures, elicitation with MJ did not have any effect, neither on tocopherol production, nor on TAT activity. These results are discussed in relation to chloroplast differentiation and the interplay between jasmonates and phytohormones.

Effect of PPG-PEG-PPG on the tocopherol-controlled release from films intended for food-packaging applications.

Science.gov (United States)

Castro López, María del Mar; Dopico García, Sonia; Ares Pernas, Ana; López Vilariño, José Manuel; González Rodríguez, María Victoria

2012-08-22

The feasibility of novel controlled release systems for the delivery of active substances from films intended for food packaging was investigated. Because polyolefins are used highly for food-packaging applications, the reported high retention degree of antioxidants has limited their use for active packaging. Thus, in this study, PP films modified with different chain extenders have been developed to favor and control the release rates of the low molecular weight antioxidant tocopherol. The use of different chain extenders as polymer modifiers (PE-PEG M(w), 575; and PPG-PEG-PPG M(w), 2000) has caused significant changes in tocopherol-specific release properties. High-performance liquid chromatography coupled to PDA-FL and PDA-MS was used to test tocopherol and chain extender migration, respectively. The release of tocopherol from the prepared films with two chain extenders into two food simulants was studied. Different temperatures and storage times were also tested. Varying the structural features of the films with the incorporation of different levels of PPG-PEG-PPG, the release of tocopherol (food-packaging additive) into different ethanolic simulants could be clearly controlled. The effect of the temperature and storage time on the release of the antioxidant has been outstanding as their values increased. The migration of the chain extender, also tested, was well below the limits set by European legislation.

Serum carotenoids, alpha-tocopherol, and lung function among Dutch elderly

NARCIS (Netherlands)

Grievink, L.; Waart, de F.G.; Schouten, E.G.; Kok, F.J.

2000-01-01

Antioxidant vitamins (provitamins) may protect against loss of lung function over time. We studied the association between serum carotenoids (-carotene, -carotene, lycopene, -cryptoxanthin, zeaxanthin, and lutein), -tocopherol, and lung function among noninstitutionalized Dutch elderly age 65 to 85

Major regression of radioinduced uterine aftereffects by pentoxifylline-tocopherol association

International Nuclear Information System (INIS)

Delanian, S.; Letur-Kornisch, H.

2000-01-01

For the young woman who wants to have a child, the association pentoxifylline-tocopherol allows to reduce the aftereffects of uterus irradiated during childhood. The endometrial and myometrial growth allows to give chance of embryo implantation. (N.C.)

Antioxidant effect of 4-nerolidylcatechol and α-tocopherol in erythrocyte ghost membranes and phospholipid bilayers

International Nuclear Information System (INIS)

Fernandes, K.S.; Silva, A.H.M.; Mendanha, S.A.; Rezende, K.R.; Alonso, A.

2013-01-01

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2′-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO 4 /H 2 O 2 , in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO 4 /H 2 O 2 , whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO 4 /H 2 O 2 . The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson’s disease

Science.gov (United States)

Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

2015-01-01

AIM: To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson’s disease (PD) rats. METHODS: Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. RESULTS: COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl- flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. CONCLUSION: COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl- secretion in the PD rat. PMID:25834315

Profile of Fatty Acids, Amino Acids, Carotenoid Total, and α-Tocopherol from Flying Fish Eggs

Directory of Open Access Journals (Sweden)

Aulia Azka

2015-12-01

Full Text Available Flying fish are found in waters of eastern Indonesia, which until now is still limited information about nutritional content. The purpose of this research was determine the composition of fatty acids, amino acids, total carotenoids, α-tocopherol flying fish eggs (Hyrundicthys sp.. The composition of fatty acid was measured by gas chromatography (GC, while amino acids, total carotenoids, α-tocopherol was measured by High performanced Liquid Chromatography (HPLC. Egg contained 22 fatty acids such as saturated fatty acid 29.71%, monounsaturated fatty acid 7.86%, and polysaturated fatty acid 13.64%. The result showed that eggs flying fish contained 17 amino acids, such as essential amino acid 14.96% and non-essential amino acids 20.27%. Eggs contained a total carotenoid of 245.37 ppm. α-tocopherol content of flying fish eggs by 1.06 ppm.

Titanocene–Gold Complexes Containing N-Heterocyclic Carbene Ligands Inhibit Growth of Prostate, Renal, and Colon Cancers in Vitro

Science.gov (United States)

2016-01-01

We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)–N-heterocyclic carbene fragments through the thiolate group: [(η5-C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold–N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer cells was demonstrated for the selected compound 5a, indicating the robustness of the heterometallic compound in vitro. We describe here preliminary mechanistic data involving studies on the interaction of selected mono- and bimetallic compounds with plasmid (pBR322) used as a model nucleic acid and the inhibition of thioredoxin reductase in PC3 prostate cancer cells. The heterometallic compounds, which are highly apoptotic, exhibit strong antimigratory effects on the prostate cancer cell line PC3. PMID:27182101

Association of serum carotenoids and tocopherols with atopic diseases in Japanese children and adolescents.

Science.gov (United States)

Okuda, Masayuki; Bando, Noriko; Terao, Junji; Sasaki, Satoshi; Sugiyama, Shinichi; Kunitsugu, Ichiro; Hobara, Tatsuya

2010-06-01

The present study assessed whether serum carotenoids and tocopherols are associated with atopic diseases (eczema and asthma) in 10- and 13-yr-olds in a Japanese community. Of 2796 students attending schools in Shunan, Japan, in 2006, 396 students were randomly selected for this study using nested case-control design. Atopic diseases and dietary food intake were assessed using self-administered questionnaires, and serum antioxidants were analyzed using high-performance liquid chromatography. We found no associations between serum carotenoids and atopic diseases. However, odds ratios (OR)s for the third and fourth quartiles of serum alpha-tocopherol with atopic eczema were 0.33 (95% confidence interval: 0.15-0.73) and 0.36 (0.14-0.89), respectively, and the trend was negatively significant (P(trend) = 0.048). We did not find a significant association for asthma. In conclusion, serum alpha-tocopherol was negatively associated with the prevalence of eczema. Serum carotenoids did not show definitive protective effects in Japanese youth.

STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH{sup +}/CD133{sup +} stem cell-like human colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Lin, Li, E-mail: lin.796@osu.edu [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States); Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Fuchs, James; Li, Chenglong [Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210 (United States); Olson, Veronica [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States); Bekaii-Saab, Tanios [Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210 (United States); Lin, Jiayuh, E-mail: lin.674@osu.edu [Center for Childhood Cancer, The Research Institute at Nationwide Children' s Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205 (United States)

2011-12-16

Highlights: Black-Right-Pointing-Pointer The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells. Black-Right-Pointing-Pointer STAT3 inhibitor, FLLL32 inhibits P-STAT3 and STAT3 target genes in colon cancer stem-like cells. Black-Right-Pointing-Pointer Inhibition of STAT3 resulted in decreased cell viability and reduced numbers of tumorspheres. Black-Right-Pointing-Pointer STAT3 is required for survival and tumorsphere forming capacity in colon cancer stem-like cells. Black-Right-Pointing-Pointer Targeting STAT3 in cancer stem-like cells may offer a novel treatment approach for colon cancer. -- Abstract: Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH{sup +}/CD133{sup +}). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower

Influence of polymer matrix and adsorption onto silica materials on the migration of alpha-tocopherol into 95% ethanol from active packaging.

Science.gov (United States)

Heirlings, L; Siró, I; Devlieghere, F; Van Bavel, E; Cool, P; De Meulenaer, B; Vansant, E F; Debevere, J

2004-11-01

In this study, the effect of polymer materials with different polarity, namely low density polyethylene (LDPE) and ethylene vinyl acetate (EVA), on the migration behaviour of alpha-tocopherol from active packaging was investigated. The antioxidant was also adsorbed onto silica materials, namely SBA-15 (Santa Barbara-15) and Syloblock, in order to protect the antioxidant during extrusion and to ensure a controlled and sufficient release during the shelf-life of the food product. Migration experiments were performed at 7.0 +/- 0.5 degrees C and 95% ethanol was used as fatty food simulant. All films contained a high concentration of alpha-tocopherol, approximately 2000 mg kg(-1), to obtain an active packaging. Polymer matrix had a small influence on the migration profile. The migration of 80% of total migrated amount of antioxidant was retarded for 2.4 days by using LDPE instead of EVA. When alpha-tocopherol was adsorbed onto both silica materials, the migration of 80% of total migrated amount of antioxidant was retarded for 3.4 days in comparison to pure alpha-tocopherol. No difference was seen between the migration profiles of alpha-tocopherol adsorbed onto both silica materials. In the case of pure alpha-tocopherol, 82% of the initial amount of alpha-tocopherol in the film migrated into the food simulant at a rather fast migration rate. In the case of adsorption on silica materials, a total migration was observed. These antioxidative films can have positive food applications.

Sensory profile of warmed-over flavour in tenderloin from steers supplemented with alpha-tocopherol

Directory of Open Access Journals (Sweden)

Moacir Evandro Lage

2012-08-01

Full Text Available The objective of the present study was to evaluate the occurrence of warmed-over flavour (WOF in cooked tenderloin and the influence of alpha-tocopherol on its inhibition. A total of 24 animals were confined, 12 of which received 1200 mg/head/day of alpha-tocopherol acetate for 90 days. Longissimus dorsi muscle cuts (tenderloin were obtained for sensory profile assessment by nine trained tasters. The tasters evaluated the taste of the meat based on four general and 18 specific attributes. The results of the evaluations were analysed with ANOVA, post-hoc tests of the means (Tukey tests, and principal component analysis (PCA. There was no significant difference in the WOF between the cuts of meat from the supplemented and non-supplemented animals. However, as the refrigeration period increased, there was a decrease in the intensity of the umami and sweet taste attributes and the flavour and aroma of the roast meat as well as an increase in the intensity of the oxidised vegetable oil flavour and the aromas of fish, hard-boiled egg, flaxseed oil, and oxidised vegetable oil. The samples that had been stored for one day were characterised by PCA as having sweet and umami tastes and the flavour and aroma of roast meat, whereas after three days, the samples were classified as having sour and bitter tastes, the flavour of chicken and nuts, and the aroma of fish. The typical sensory attributes desirable for roasted meat decreased in intensity during the three days of storage after cooking, whereas the intensity of unpleasant (oxidative attributes for the consumer increased.

PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

Energy Technology Data Exchange (ETDEWEB)

Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch; Demartines, Nicolas, E-mail: Demartines@chuv.ch; Dormond, Olivier, E-mail: Olivier.dormond@chuv.ch

2014-09-05

Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 2} directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 2} increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 2} increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

Influence of soy protein’s structural modifications on their microencapsulation properties: a-tocopherol microparticles preparation

OpenAIRE

Nesterenko, Alla; Alric, Isabelle; Silvestre, Françoise; Durrieu, Vanessa

2012-01-01

Enzymatic and chemical modifications of soy protein isolate (SPI) were studied in order to improve SPI properties for their use as wall material for a-tocopherol microencapsulation by spray-drying. The structural modifications of SPI by enzymatic hydrolysis and/or N-acylation were carried out in aqueous media without any use of organic solvent neither surfactant. Emulsions from aqueous solutions of native or modified SPI and hydrophobic a-tocopherol, were prepared and spray-dri...

Effects of omega-3 fatty acid plus alpha-tocopherol supplementation on malnutrition-inflammation score, biomarkers of inflammation and oxidative stress in chronic hemodialysis patients.

Science.gov (United States)

Asemi, Zatollah; Soleimani, Alireza; Shakeri, Hossein; Mazroii, Navid; Esmaillzadeh, Ahmad

2016-11-01

The current study was carried out to assess the effects of omega-3 fatty acid and alpha-tocopherol co-supplementation on malnutrition-inflammation score (MIS), biomarkers of inflammation and oxidative stress in chronic hemodialysis (HD) patients. In a randomized double-blind placebo-controlled clinical trial, 120 patients with chronic HD were included. Patients were randomly allocated into four groups to receive: (1) 1250 mg/day omega-3 fatty acid containing 600 mg EPA and 300 mg DHA + alpha-tocopherol placebo (n = 30); (2) 400 IU/day alpha-tocopherol + omega-3 fatty acids placebo (n = 30); (3) 1250 mg omega-3 fatty acids/day + 400 IU/day alpha-tocopherol (n = 30); and (4) omega-3 fatty acids placebo + alpha-tocopherol placebo (n = 30) for 12 weeks. After 12 weeks of intervention, all three groups of alpha-tocopherol only, individual omega-3 fatty acids, and combined omega-3 fatty acids and alpha-tocopherol experienced a significant improvements in MIS compared with the placebo group; however, improvements were much greater in the individual omega-3 fats (-1.4 ± 1.4) and combined omega-3 fats and alpha-tocopherol (-1.1 ± 2.3) groups compared with alpha-tocopherol group alone (-0.5 ± 1.7, P = 0.004). Furthermore, both individual and combined intervention with omega-3 fats and alpha-tocopherol led to a significant increase in plasma nitric oxide (NO) (combined group: +17.6 ± 29.3; alpha-tocopherol: +43.1 ± 36.3; omega-3 fats: +31.0 ± 40.0; and placebo: -0.5 ± 18.5 µmol/L, respectively, P acids and alpha-tocopherol co-supplementation for 12 weeks among HD patients improved MIS, plasma NO and TAC levels. Future studies with longer duration of the intervention are needed to confirm the validity of our findings. CLINICAL REGISTRATION: www.irct.ir as IRCT201410245623N28.

The influence of androgens, anti-androgens, and castration on cell proliferation in the jejunal and colonic crypt epithelia, and in dimethylhydrazine-induced adenocarcinoma of rat colon.

Science.gov (United States)

Tutton, P J; Barkla, D H

1982-01-01

Androgenic hormones have previously been shown to promote cell proliferation in the small intestine of rat and androgen receptors have been demonstrated in carcinomata of the large intestine of rat. In this study the influence of testosterone and of castration on epithelial cell proliferation in the small intestine, the large intestine and in dimethylhydrazine-induced colonic tumours is compared. Cell proliferation in the small intestine and in colonic tumours was accelerated by testosterone treatment, and cell proliferation in colonic tumours, but not in the small intestine, was retarded following castration. Cell proliferation in colonic tumours was also inhibited by the anti-androgenic drug, Flutamide. Testosterone and castration each failed to influence cell proliferation in the colonic crypt epithelium of both normal and carcinogen-treated animals.

Molecular cloning, heterologous expression and functional characterization of gamma tocopherol methyl transferase (γ-TMT) from Glycine max.

Science.gov (United States)

Tewari, Kalpana; Dahuja, Anil; Sachdev, Archana; Kumar, Vaibhav; Ali, Kishwar; Kumar, Amresh; Kumari, Sweta

2017-12-01

γ-Tocopherol methyltransferase (γ-TMT) (EC 2.1.1.95) is the last enzyme in the tocopherol biosynthetic pathway and it catalyzes the conversion of γ-tocopherol into α-tocopherol, the nutritionally significant and most bioactive form of vitamin E. Although the γ-TMT gene has been successfully overexpressed in many crops to enhance their α-tocopherol content but still only few attempts have been made to uncover its structural, functional and regulation aspects at protein level. In this study, we have cloned the complete 909bp coding sequence of Glycine max γ-TMT (Gm γ-TMT) gene that encodes the corresponding protein comprising of 302 amino acid residues. The deduced Gm γ-TMT protein showed 74-87% sequence identity with other characterized plant γ-TMTs. Gm γ-TMT belongs to Class I Methyl Transferases that have a Rossmann-like fold which consists of a seven-stranded β sheet joined by α helices. Heterologous expression of Gm γ-TMT in pET29a expression vector under the control of bacteriophage T7 promoter produced a 37.9 kDa recombinant Gm γ-TMT protein with histidine hexamer tag at its C-terminus. The expression of recombinant Gm γ-TMT protein was confirmed by western blotting using anti-His antibody. The recombinant protein was purified by Ni 2+ -NTA column chromatography. The purified protein showed SAM dependent methyltransferase activity. The α-tocopherol produced in the in-vitro reaction catalyzed by the purified enzyme was detected using reverse phase HPLC. This study has laid the foundation to unveil the biochemical understanding of Gm γ-TMT enzyme which can be further explored by studying its kinetic behaviour, substrate specificity and its interaction with other biomolecules. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterisation of fatty acid, carotenoid, tocopherol/tocotrienol compositions and antioxidant activities in seeds of three Chenopodium quinoa Willd. genotypes.

Science.gov (United States)

Tang, Yao; Li, Xihong; Chen, Peter X; Zhang, Bing; Hernandez, Marta; Zhang, Hua; Marcone, Massimo F; Liu, Ronghua; Tsao, Rong

2015-05-01

Composition of fatty acids, tocopherols, tocotrienols, and carotenoids, and their contribution to antioxidant activities were investigated in seeds of three coloured quinoa cultivars (white, red and black). The major components and individual compounds were significantly different, and their concentrations were higher in darker seeds (p tocopherol content ranged from 37.49 to 59.82 μg/g and mainly consisted of γ-tocopherol. Trace amount of α- and β-tocotrienols was also found. Black quinoa had the highest vitamin E followed by red and white quinoas. Carotenoids, mainly trans-lutein (84.7-85.6%) and zeaxanthin were confirmed for the first time in quinoa seeds, and the concentration was also the highest in black seeds. The antioxidant activities of lipophilic extracts were positively correlated with polyunsaturated fatty acids, total carotenoids and total tocopherols. Copyright © 2014. Published by Elsevier Ltd.

Value-added potential of expeller-pressed canola oil refining: characterization of sinapic acid derivatives and tocopherols from byproducts.

Science.gov (United States)

Chen, Yougui; Thiyam-Hollander, Usha; Barthet, Veronique J; Aachary, Ayyappan A

2014-10-08

Valuable phenolic antioxidants are lost during oil refining, but evaluation of their occurrence in refining byproducts is lacking. Rapeseed and canola oil are both rich sources of sinapic acid derivatives and tocopherols. The retention and loss of sinapic acid derivatives and tocopherols in commercially produced expeller-pressed canola oils subjected to various refining steps and the respective byproducts were investigated. Loss of canolol (3) and tocopherols were observed during bleaching (84.9%) and deodorization (37.6%), respectively. Sinapic acid (2) (42.9 μg/g), sinapine (1) (199 μg/g), and canolol (344 μg/g) were found in the refining byproducts, namely, soap stock, spent bleaching clay, and wash water, for the first time. Tocopherols (3.75 mg/g) and other nonidentified phenolic compounds (2.7 mg sinapic acid equivalent/g) were found in deodistillates, a byproduct of deodorization. DPPH radical scavenging confirmed the antioxidant potential of the byproducts. This study confirms the value-added potential of byproducts of refining as sources of endogenous phenolics.

SGD1, a key enzyme in tocopherol biosynthesis, is essential for plant development and cold tolerance in rice.

Science.gov (United States)

Wang, Di; Wang, Yunlong; Long, Wuhua; Niu, Mei; Zhao, Zhigang; Teng, Xuan; Zhu, Xiaopin; Zhu, Jianping; Hao, Yuanyuan; Wang, Yongfei; Liu, Yi; Jiang, Ling; Wang, Yihua; Wan, Jianmin

2017-07-01

Tocopherols, a group of Vitamin E compounds, are essential components of the human diet. In contrast to well documented roles in animals, the functions of tocopherols in plants are less understood. In this study, we characterized two allelic rice dwarf mutant lines designated sgd1-1 and sgd1-2 (small grain and dwarf1). Histological observations showed that the dwarf phenotypes were mainly due to cell elongation defects. A map-based cloning strategy and subsequent complementation test showed that SGD1 encodes homogentisate phytyltransferase (HPT), a key enzyme in tocopherol biosynthesis. Mutation of SGD1 resulted in tocopherol deficiency in both sgd1mutants. No oxidant damage was detected in the sgd1 mutants. Further analysis showed that sgd1-2 was hypersensitive to cold stress. Our results indicate that SGD1 is essential for plant development and cold tolerance in rice. Copyright © 2017 Elsevier B.V. All rights reserved.

Low concentration of copper inhibits colonization of soil by the arbuscular mycorrhizal fungus Glomus intraradices and radically changes the microbial community structure

DEFF Research Database (Denmark)

Hagerberg, David; Manique, Nina; Brandt, Kristian K.

2011-01-01

. To avoid indirect effects through the plant, copper was only added to root-free microcosm compartments. [Cu]bio was measured using a Pseudomonas fluorescens biosensor strain. In the range of 0–1.5 μg g−1 [Cu]bio, a log–log linear relationship between added copper and [Cu]bio was found. Microbial...... colonization of the root-free compartment was evaluated by whole-cell fatty acid analysis (WCFA) and amplified rDNA restriction analysis (ARDRA). The WCFA analysis showed that the AM fungus soil colonization was severely inhibited by Cu with a 50% reduction of mycorrhizal growth at 0.26 μg g−1 [Cu......]bio. The growth of other main microbial groups was not significantly affected by copper. However, ARDRA analysis showed a very strong effect of copper on the bacterial community composition probably caused by an increased proportion of Cu-resistant bacteria. Our results suggest that problems with plant yield may...

Down-regulation of LRP1B in colon cancer promoted the growth and migration of cancer cells.

Science.gov (United States)

Wang, Zhiqiang; Sun, Peng; Gao, Chun; Chen, Ji; Li, Jun; Chen, Zhonghao; Xu, Ming; Shao, Jun; Zhang, Yunpeng; Xie, Jiang

2017-08-01

Aberrant activation of beta-catenin/TCF signaling is one of the hallmarks of colon cancer. It is of great interest to study the mechanism for the regulation of beta-catenin/TCF signaling. In this study, it was found that LRP1B was down-regulated in colon cancer tissues and inhibited the growth, migration and metastasis of colon cancer cells. The molecular mechanism study revealed that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling. Taken together, our study demonstrated the suppressive roles of LRP1B in the progression of colon cancer, implicating that restoring the function of LRP1B would be a promising strategy for the treatment of colon cancer. Copyright © 2017. Published by Elsevier Inc.

Effectiveness of Dry Cow Therapy Comprising Antibiotic Treatment, Internal Teat Sealant, and α-Tocopherol Against New Intramammary Infections in Cows

Directory of Open Access Journals (Sweden)

Cengiz Mehmet

2015-04-01

Full Text Available The aim of this study was to evaluate the preventive effectiveness of dry cow therapy based on antibiotic, internal teat sealant, and α-tocopherol administered separately or in various combinations at drying-off The study was performed on 322 uninfected quarters of 95 cows originating from three dairy herds. The new intramammary infection rates after calving were measured to evaluate the effectiveness. The quarters were divided into six groups differing in treatment, namely: control group (group C, n = 40 and five treatment groups. Treatment groups were arranged as follows: group A (antibiotic alone, n = 81, group AS (antibiotic + sealant, n = 40, group AST (antibiotic + sealant + α-tocopherol, n = 40, group T (α-tocopherol alone, n = 40, group S (sealant alone, n = 81. New infection rate amounted to 47.5% in group C. The treatment in group AST significantly prevented from the occurrence of new intramammary infections (12.5%, P 0.05, although the use of the sealant alone (group S decreased the risk of new infection (24.7%, P 0.05. Increased α-tocopherol level (P < 0.05 was detected after calving in the quarters from cows that received α-tocopherol injections. In conclusion, the combination of antibiotic, internal teat sealant, and α-tocopherol used in dry cow therapy showed a significantly better preventive effect against new intramammary infections, than the therapeutics administered separately.

Changes in colonic motility induced by sennosides in dogs: evidence of a prostaglandin mediation.

OpenAIRE

Staumont, G; Fioramonti, J; Frexinos, J; Bueno, L

1988-01-01

The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter and a polyethylene catheter implanted in a branch of the right colonic artery. Oral sennosides (30 mg/kg) inhibited colonic motility for 12 to 18 h after a three to six hours delay, and associated with giant contractions and diarrhoea. The minimal oral dose of sennosides to produce such changes var...

Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid

DEFF Research Database (Denmark)

Meyer, Anne Merete Boye; Jacobsen, Charlotte Munch

1996-01-01

Meyer, A. S. & C. Jacobsen, 1996. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid, J. Food Lipids, 3, 139-147.......Meyer, A. S. & C. Jacobsen, 1996. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid, J. Food Lipids, 3, 139-147....

Miscibility of dl-α-tocopherol β-glucoside in DPPC monolayer at air/water and air/solid interfaces

Energy Technology Data Exchange (ETDEWEB)

Neunert, G. [Department of Physics and Biophysics, Poznan University of Life Sciences, 60-637 Poznan (Poland); Makowiecki, J.; Piosik, E.; Hertmanowski, R. [Faculty of Technical Physics, Poznan University of Technology, 60-965 Poznan (Poland); Polewski, K. [Department of Physics and Biophysics, Poznan University of Life Sciences, 60-637 Poznan (Poland); Martynski, T., E-mail: tomasz.martynski@put.poznan.pl [Faculty of Technical Physics, Poznan University of Technology, 60-965 Poznan (Poland)

2016-10-01

The role of newly synthesized tocopherol glycosidic derivative in modifying molecular organization and phase transitions of phospholipid monolayer at the air/water interface has been investigated. Two-component Langmuir films of dl-α-tocopheryl β-D-glucopyranoside (BG) mixed with dipalmitoyl phosphatidylcholine (DPPC) in the whole range of mole fractions were formed at the water surface. An analysis of surface pressure versus mean molecular area (π-A) isotherms and Brewster angle microscope images showed that the presence of BG molecules changes the structure and packing of the DPPC monolayer in a BG concentration dependent manner. BG molecules incorporated into DPPC monolayer inhibit its liquid expanded to liquid condensed phase transition proportionally to the BG concentration. The monolayers were also transferred onto solid substrates and visualized using an atomic force microscope. The results obtained indicate almost complete miscibility of BG and DPPC in the monolayers at surface pressures present in the biological cell membrane (30-35·10{sup -3} N·m{sup -1}) for a BG mole fraction as high as 0.3. This makes the monolayer less packed and more disordered, leading to an increased permeability. The results support our previous molecular dynamics simulation data. - Highlights: • Langmuir films of α-tocopherol derivative with DPPC was studied thermodynamically. • Mixed DPPC/BG films were transferred onto mica substrates for topography imaging by using AFM. • Miscibility of BG/DPPC films at surface pressures present in membranes was observed up to MF = 0.3.

Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

Energy Technology Data Exchange (ETDEWEB)

Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China); Dong, Wei-Guo, E-mail: dongwg1966@yahoo.com.cn [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province (China)

2012-05-11

Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.

PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells.

Science.gov (United States)

Raab, Monika; Sanhaji, Mourad; Matthess, Yves; Hörlin, Albrecht; Lorenz, Ioana; Dötsch, Christina; Habbe, Nils; Waidmann, Oliver; Kurunci-Csacsko, Elisabeth; Firestein, Ron; Becker, Sven; Strebhardt, Klaus

2018-03-16

The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities. The inhibition of PLK1 in mitotic, APC-∆C-expressing cells reduces the kinetochore levels of Aurora B and hampers the recruitment of SAC component suggesting a compromised mitotic checkpoint. Furthermore, Plk1 inhibition (RNAi, pharmacological compounds) promotes the development of adenomatous polyps in two independent Apc Min/+ mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly.

Capecitabine treatment of HCT-15 colon cancer cells induces ...

African Journals Online (AJOL)

HCT-15 cells caused condensation of DNA and induced apoptosis in a concentration- ... Conclusion: Capecitabine treatment causes inhibition of colon cancer growth via the mitochondrial ... fluoropyrimidine aimed to selectively transfer 5-.

Absorption and transport of deuterium-substituted 2R,4'R,8'R-alpha-tocopherol in human lipoproteins

International Nuclear Information System (INIS)

Traber, M.G.; Ingold, K.U.; Burton, G.W.; Kayden, H.J.

1988-01-01

Oral administration of a single dose of tri- or hexadeuterium substituted 2R,4'R,8'R-alpha-tocopheryl acetate (d3- or d6-alpha-T-Ac) to humans was used to follow the absorption and transport of vitamin E in plasma lipoproteins. Three hr after oral administration of d3-alpha-T-Ac (15 mg) to 2 subjects, plasma levels of d3-alpha-T were detectable; these increased up to 10 hr, reached a plateau at 24 hr, then decreased. Following administration of d6-alpha-T-Ac (15-16 mg) to 2 subjects, the percentage of deuterated tocopherol relative to the total tocopherol in chylomicrons increased more rapidly than the corresponding percentage in whole plasma. Chylomicrons and plasma lipoproteins were isolated from 2 additional subjects following administration of d3-alpha-T-Ac (140 or 60 mg). The percentage of deuterated tocopherol relative to the total tocopherol increased most rapidly in chylomicrons, then in very low density lipoproteins (VLDL), followed by essentially identical increases in low and high density lipoproteins (LDL and HDL, respectively) and lastly, in the red blood cells. This pattern of appearance of deuterated tocopherol is consistent with the concept that newly absorbed vitamin E is secreted by the intestine into chylomicrons; subsequently, chylomicron remnants are taken up by the liver from which the vitamin E is secreted in VLDL. The metabolism of VLDL in the circulation results in the simultaneous delivery of vitamin E into LDL and HDL

Assessing the Fatty Acid, Carotenoid, and Tocopherol Compositions of Amaranth and Quinoa Seeds Grown in Ontario and Their Overall Contribution to Nutritional Quality.

Science.gov (United States)