Different Forms Of Vitamin Research Articles

Serum free 1,25-dihydroxy-vitamin D is more closely associated with fibroblast growth factor 23 than other vitamin D forms in chronic dialysis patients

BackgroundMineral bone disorder (MBD) is prevalent among chronic dialysis patients. However, relationship between different forms of vitamin D and fibroblast growth factor 23 (FGF-23) remains unclear in this population. MethodsA multicenter hemodialysis cohort was assembled. We evaluated 25-OH-D and 1,25-(OH)2-D, vitamin D-binding protein, and FGF-23, in this cohort. Multiple regression analyses were performed to investigate the relationship and stewardship between different vitamin D forms and FGF-23 concentrations. ResultsChronic dialysis patients presented significantly higher FGF-23 concentrations. 25-OH-D concentrations of <20ng/ml (deficiency), 20–30ng/ml (insufficiency), and ≥30ng/ml (sufficiency) were associated with progressively lower FGF-23 concentrations (p<0.01). Serum FGF-23 concentrations were significantly correlated with total (p=0.02), free (p<0.01) and bioavailable (p<0.01) 25-OH-D and total (p=0.04), free (p=0.02), and bioavailable (p=0.03) 1,25-(OH)2-D concentrations. With all 25-OH-D and 1,25-(OH)2-D forms in the regression model, we found that free 1,25-(OH)2-D outweighed all other vitamin D forms regarding its association with FGF-23 (p=0.03). ConclusionThe relationship between FGF-23 and vitamin D is stronger using free forms of 25-OH-D and 1,25-(OH)2-D. Subsequent studies aiming at MBD should consider including free 25-OH-D and 1,25-(OH)2-D in the analysis.

Confusions in Vitamin D Estimation and Interpretation

Role of vitamin D in calcium and phosphorous regulation and in bone metabolism is a well known fact and so, was the need for diagnosing vitamin D deficiency in osteoporosis, osteomalacia and fractures. Discovery of the presence of vitamin D receptor in several tissues has lead to several research works to know the effect of vitamin D on these tissues. This has thrown light on previously blind areas. Vitamin D deficiency is known to be present in cancers, infectious diseases, autoimmune disorders,cardiovascular disease type 2 diabetes mellitus. These findings have resulted in increased laboratory requests for vitamin D estimation. This article aims at providing insight 1. into vitamin D and its metabolic effects , 2.different forms of vitamin D 3.existing methods to estimate vitamin D 4. Selection of the method for estimation, and reference methods for vitamin D estimation, 5. Factors causing variations in vitamin D results, 6. internal and external quality control issues,7.Interpretation of results.

Recent Trends in The Determination of Vitamin D

The occurrence of vitamin D deficiency has become an issue of serious concern in the worldwide population. As a result numerous analytical methods have been developed, for a variety of matrices, during the last few years to measure vitamin D analogs and metabolites. This review employs a comprehensive search of all vitamin D methods developed during the last 5 years for all applications, using ISI Web of Science(®), Scifinder(®), Science Direct, Scopus and PubMed. Particular emphasis is given to sample-preparation methods and the different forms of vitamin D measured across different fields of applications such as biological fluids, food and pharmaceutical preparations. This review compares and critically evaluates a wide range of approaches and methods, and hence it will enable readers to access developments across a number of applications and to select or develop the optimal analytical method for vitamin D for their particular application.

Bioavailability of Vitamin D2and D3in Healthy Volunteers, a Randomized Placebo-Controlled Trial

The bioequivalence of the different forms of vitamin D, ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), has been questioned. Earlier studies have suggested that vitamin D2 is less biologically active than vitamin D3.In a parallel study, we tested the effects of supplementation with 50-μg/d doses of vitamin D2 or D3 or a placebo over a period of 8 weeks on 25(OH)D2, 25(OH)D3, their sum 25(OH)D (primary outcome variables), and PTH in healthy volunteers applying a double-blind, randomized study design. The study was conducted during the winter of 2012 in Halle (Saale), Germany, at latitude 51°47N, when UVB irradiation is virtually absent. Blood samples for the determinations of vitamin D status and PTH were collected at baseline and after 4 and 8 weeks of supplementation.In the placebo group (n = 19), 25(OH)D3 decreased from 39.4 ± 14.2 to 31.1 ± 12.4 nmol/L after 8 weeks (P < .01). In the vitamin D3 group (n = 42), the concentrations of 25(OH)D3 increased from 41.5 ± 22.8 nmol/L at baseline to 88.0 ± 22.1 nmol/L after 8 weeks (P < .01). In the group receiving vitamin D2 (n = 46), the 25(OH)D2 concentrations increased significantly, whereas the 25(OH)D3 concentration fell from 36.4 ± 13.3 nmol/L at baseline to 16.6 ± 6.3 nmol/L after 8 weeks (P < .01). The total 25(OH)D was not different between the groups at baseline but differed significantly between the groups after 4 and 8 weeks (P < .001).Vitamin D3 increases the total 25(OH)D concentration more than vitamin D2. Vitamin D2 supplementation was associated with a decrease in 25(OH)D3, which can explain the different effect on total 25(OH)D.

Vitamin E Secretion by Caco-2 Monolayers to APOA1, but Not to HDL, Is Vitamer Selective1,2

The aim of this study was to characterize the pathways of basolateral secretion of common dietary tocopherols from polarized Caco-2 monolayers, a model of intestinal absorption. Given differences in structure and physical properties, we hypothesized that secretion may differ between different forms of vitamin E, thus potentially contribute to the selectivity seen in vivo. Monolayers were incubated apically and simultaneously with 10 μmol/L α-, γ-, and δ-tocopherol (1:1:1) in lipid micelles. Treatment with the microsomal triglyceride transfer protein inhibitor BMS201038 revealed that the triglyceride-rich particle secretory pathway (apolipoprotein B–dependent pathway) accounted for ∼80% of total tocopherol secretion, without selectivity among the three forms of vitamin E. Apolipoprotein B–independent secretion of tocopherols (and cholesterol) was greatly enhanced by the liver X receptor agonist T0901317. T0901317 induced ATP-binding cassette transporter A1 (ABCA1) protein expression and basolateral secretion of tocopherols to apolipoprotein A1. ABCA1-dependent secretion demonstrated vitamer selectivity such that efficiency of secretion of α- and γ-tocopherols exceeded that of δ-tocopherol. Basal addition of HDL stimulated vitamin E secretion but without selectivity among the three forms, whereas LDL had no effect. Basal addition of scavenger receptor class B member I (SR-BI) blocking antibody, which inhibits the interaction between SR-BI and HDL, increased basal accumulation of all tocopherols, demonstrating a role for SR-BI in cellular re-uptake of secreted vitamin E. These findings demonstrated that vitamin E and cholesterol utilize common pathways of secretion and that secretion via the ABCA1 pathway favors certain forms of vitamin E.

Dietary Antioxidants and Prostate Cancer: A Review

Prostate cancer is the most common noncutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, whereas lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms.

Effects of dietary vitamin C and soybean lecithin in the nutrition of brown bullhead (Ameiurus nebulosus L.) fingerlings

The effects of different forms of vitamin C and soybean lecithin on growth performance, feed utilization and body composition of brown bullhead (Ameiurus nebulosus, Lesuer 1819) were evaluated during a 9-week growth trial. A special interest was to investigate a possible combine effect of these nutritional components. The diets used contained three forms of vitamin C (crystallized ascorbic acid, encapsulated L-ascorbic acid and Ca-L-threonate) (100 mg/kg) with and without the combination of soybean lecithin. Besides control diet (K), one more diet was supplemented with soybean lecithin (L) only. One-hundred-ninety-two brown bullhead of about 45 g initial body weight was randomly divided in 24 tanks (115 L each). Testing conditions included 8 fish per tank, with triplicate tanks for treatment. All diets with supplemented components had higher final weight. Specific growth rate, feed conversion rate and condition factor were significantly higher with encapsulated vitamin C diets (CC, CCL), followed by the results of enriched ascorbic acid diets. Vitamin C and lecithin supplementation showed positive influence on significantly higher number of erythrocytes, haematocrit, triglycerides and total protein. Vitamin C content of muscle and liver tissue was not uniform and was significantly higher in AAL, CCL, CC and AA feeding groups. The fatty acids profile of muscle and liver tissue showed that phospholipids from soybean lecithin and vitamin C diets enhanced the quality of usable part of the fish body. Combine supplementation of vitamin C and soy lecithin indicated positive production effects, but did not cause a statistically significant difference.

Effects of Dietary Vitamin C and Soybean Lecithin in the Nutrition of Brown Bullhead (Ameiurus Nebulosus L.) Fingerlings

The effects of different forms of vitamin C and soybean lecithin on growth performance, feed utilization and body composition of brown bullhead (Ameiurus nebulosus, Lesuer 1819) were evaluated during a 9-week growth trial. A special interest was to investigate a possible combine effect of these nutritional components. The diets used contained three forms of vitamin C (crystallized ascorbic acid, encapsulated L-ascorbic acid and Ca-L-threonate) (100 mg/kg) with and without the combination of soybean lecithin. Besides control diet (K), one more diet was supplemented with soybean lecithin (L) only. One-hundred-ninety-two brown bullhead of about 45 g initial body weight was randomly divided in 24 tanks (115 L each). Testing conditions included 8 fish per tank, with triplicate tanks for treatment. All diets with supplemented components had higher final weight. Specific growth rate, feed conversion rate and condition factor were significantly higher with encapsulated vitamin C diets (CC, CCL), followed by the results of enriched ascorbic acid diets. Vitamin C and lecithin supplementation showed positive influence on significantly higher number of erythrocytes, haematocrit, triglycerides and total protein. Vitamin C content of muscle and liver tissue was not uniform and was significantly higher in AAL, CCL, CC and AA feeding groups. The fatty acids profile of muscle and liver tissue showed that phospholipids from soybean lecithin and vitamin C diets enhanced the quality of usable part of the fish body. Combine supplementation of vitamin C and soy lecithin indicated positive production effects, but did not cause a statistically significant difference.

Supplementation with Natural Forms of Vitamin E Augments Antigen-Specific TH1-Type Immune Response to Tetanus Toxoid

This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol (α-T), and delta-tocotrienol (δ-T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56) to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P < 0.05) in mice that were fed with δ-T3 or TRF compared to controls. The production of IFN-γ and IL-4 by splenocytes from the vitamin E treated mice was significantly (P < 0.05) higher than that from controls. The IFN-γ production was the highest in animals supplemented with δ-T3 followed by TRF and finally α-T. Production of TNF-α was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with δ-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1) immune response.

Distinct roles of different forms of vitamin E in DHA‐induced apoptosis in triple‐negative breast cancer cells

Docosahexaenoic acid (DHA) has been shown to exhibit anticancer actions in vitro and in vivo in a variety of cancers. Here, we investigated the role for DHA in inducing apoptosis in triple-negative breast cancer (TNBC) and studied the mechanisms of action. DHA induces apoptosis as detected by Annexin V-FITC/PI assay as well as induces cleavage of caspase-8 and -9, endoplasmic reticulum stress (ERS), and elevated levels of death receptor-5 (DR5) protein expression as detected by western blot assays. Chemical inhibitors of caspase-8 and -9 and small interfering RNAs (siRNAs) show DHA to induce ERS/CHOP/DR5-mediated caspase-8 and -9 dependent apoptosis. Furthermore, DHA induces elevated cellular levels of reactive oxygen species (ROS) and antioxidant; RRR-α-tocopherol (αT) blocked DHA-induced apoptotic events. In contrast to the antagonistic impact of αT, gamma-tocotrienol (γT3) was demonstrated to cooperate with DHA in inducing apoptotic events in TNBC cells. Data, for the first time, demonstrate that DHA induces apoptosis in TNBC cells via activation of ERS/CHOP/DR5-mediated caspase-8 and -9 dependent pro-apoptotic events, and that different forms of vitamin E exhibit distinct effects on DHA-induced apoptosis; namely, inhibition by αT and enhancement by γT3.

Abstract 4953: Interaction of vitamin E compounds with docosahexaenoic acid on induction of apoptosis in human triple negative breast cancer cells

Abstract Successful treatment of triple negative (ER-, PR-, HER2-) breast cancers (TNBC) remains elusive because of the limitations of currently available chemotherapeutic agents for TNBC, drug resistance and drug toxicities. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, has been shown to exhibit anticancer actions both in vitro and in vivo in a variety of cancers, including human breast cancer. Here, we report that DHA induces apoptosis in TNBC cell lines, which is associated with cleavage of caspase-8 and -9. DHA induces endoplasmic reticulum (ER) stress evidenced by the increased levels of ER stress markers, GRP78, CHOP, and spliced XBP-1, and induced increased levels of death receptor DR5 protein expression. siRNAs to CHOP and DR5 blocked DHA-induced apoptosis and siRNA to CHOP blocked DHA-induced upregulation of DR5, indicating that DHA induces ER stress mediated death receptor dependent apoptosis in TNBC cells via CHOP. Furthermore, our data show that DHA mediated increases in levels of reactive oxygen species (ROS), apoptosis and ER stress can be blocked by antioxidants; N-Acetyl Cysteine (NAC) and alpha-tocopherol (αT) indicating that ROS plays a critical role in DHA-induced apoptosis and ER stress. In contrast to αT, gamma-tocotrienol (γT3), another form of vitamin E, cooperated with DHA to induce apoptosis and ER stress in TNBC cells. siRNAs to CHOP and DR5 blocked the combination effects mediated by DHA + γT3 on induction of apoptosis and ER stress. Taken together, our data, for the first time, demonstrate that DHA induces apoptosis in TNBC cells via activation of an ER stress mediated DR5 dependent pro-apoptotic pathway. Our data also show that different forms of vitamin E exhibit different combinational effects on DHA-induced apoptosis; namely, blockage by αT and enhancement by γT3. (Funding for these studies was provided by the Clayton Foundation for Research). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4953. doi:1538-7445.AM2012-4953

Role of vitamin d in Parkinson's disease.

Parkinson's disease (PD) is the second most common form of neurodegeneration in the elderly population. Clinically, it is characterized by tremor, rigidity, slowness of movement, and postural imbalance. A significant association between low serum vitamin D and PD has been demonstrated, suggesting that elevated vitamin D levels might provide protection against PD. Genetic studies have helped identify a number of proteins linking vitamin D to PD pathology, including the major histocompatibility complex (MHC) class II, the vitamin D receptor (VDR), cytochrome P450 2D6 (CYP2D6), chromosome 22, the renin-angiotensin system (RAS), heme oxygenase-1 (HO-1), poly(ADP-ribose) polymerase-1 gene (PARP-1), neurotrophic factor (NTF), and Sp1 transcription factor. Vitamin D has also been implicated in PD through its effects on L-type voltage-sensitive calcium channels (L-VSCC), nerve growth factor (NGF), matrix metalloproteinases (MMPs), prostaglandins (PGs) and cyclooxygenase-2 (COX-2), reactive oxygen species (ROS), and nitric oxide synthase (NOS). A growing body of evidence suggests that vitamin D supplementation may be beneficial for PD patients. Among the different forms of vitamin D, calcitriol (1,25-dihydroxyvitamin D3) is best indicated for PD, because it is a highly active vitamin D3 metabolite with an appropriate receptor in the central nervous system (CNS).

On the Mechanism of Synergistic Cytotoxicity of Vitamins C and K3: Experiments in Vitro and Quantum-Chemical Analysis

Most patients with hepatocellular carcinoma are inoperable and hepatoma cells are resistant to conventional chemotherapies. So, it is important to develop novel therapies. Treatment of mouse hepatoma MH-22A cells by vitamins C and K3 at the ratio of 100:1 greatly enhanced their cytotoxicity. When cells were subjected to vitamin C at 200 μM or K3 at 2 μM separately, viability was more than 90%. However, when vitamins C and K3 were combined at these concentrations, less than 10% of cells survived.To elucidate the mechanism of this synergy, theoretical quantum-chemical analysis of the dynamics of intermolecular electron transfer (IET) processes within the complexes containing C and K3 was carried out. Optimization of the ground state complex geometry was provided by means of GAUSSIAN03 package. Simulation of the IET was done using NUVOLA package, in the framework of molecular orbitals. Rate of IET was calculated using Fermi Golden rule.Two concurrent pathways of a plausible mechanism of the synergistic action of vitamins C and K3 were analyzed: increasing of acidity in the near surrounding of complex significantly affects redox-cycling and creating the most stable [C2K] complex stabilizes acidity at a high level.Out of the complexes of vitamin K3 with five different forms of vitamin C, the most stable one was the complex with de-hydro-ascorbic acid [C2K], and the second one - with ascorbic acid [C1K]. The spectra of IET represent the different nature of complexes. There are several possibilities for electron transfer in the less stable [C1K] complex, while for the most stable [C2K] complex; the number of resonant states significantly decreases. This confirms that the creation of complex [C1K] escalates increasing of acidity.

Intoxicación por sobredosificación de vitamina D en un lactante

The objective of this technical note describes and comments on a recent clinical case of poisoning by overdose of vitamin D, and the correct interpretation of clinical and laboratory parameters. Vitamin D is a fat-soluble vitamin involved in the absorption of calcium and phosphorus in the intestine. Administration of high doses for prolonged periods can cause hypercalcemia, leading to kidney failure and renal calcifications. Clinical caseMale, 6 months old in treatment with Biominol® (vitamin D supplement), was admitted to the emergency department because of a state of decline and irritability. The initial analytical results showed an ionized calcium concentration in blood of 2.11mmol/L (reference interval (RI): 1.15 - 1.29mmol/L), and plasma total calcium concentration of 5.5mmol/L (RI: 2.25–2.75mmol/L). In our laboratory, Vitamin D2 and D3 were determined by liquid chromatography high resolution (HPLC), and an electrochemiluminescence method. The results showed a vitamin D2 419ng/mL and total vitamin D 482ng/mL (RI: 30–100ng/mL). It was found that the vitamin D overdose was of exogenous origin, due to increased vitamin D2.The definitive diagnosis of this patient was severe hypercalcemia secondary to exogenous vitamin D poisoning, and nephrocalcinosis secondary to this with normal renal function with hypercalciuria.In conclusion, the correct dosing of patients and determination of different forms of vitamin D to trace its origin and making a correct interpretation is important.

Interconversions of different forms of vitamin B 6 in tobacco plants

There are six different vitamin B 6 (VB 6) forms, pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), pyridoxal 5′-phosphate (PLP), pyridoxamine 5′-phosphate (PMP), and pyridoxine 5′-phosphate (PNP), of which PLP is the active form. Although plants are a major source of VB 6 in the human diet, and VB 6 plays an important role in plants, the mechanisms underlying the interconversions of different VB 6 forms are not well understood. In this study, in vitro tobacco plants were grown on Murashige and Skoog (MS) basal media supplemented with 100 mg/L of PM, PL or PN and the abundance of the different B 6 vitamers in leaf tissue was quantified by high performance liquid chromatography (HPLC). The total amount of VB 6 was about 3.9 μg/g fresh weight of which PL, PM, PN, PLP and PMP accounted for 23%, 14%, 37%, 20% and 6%, respectively. Tobacco plants contained a trace amount of PNP. Supplementation of the culture medium with any of the non-phosphorylated vitamers resulted in an increase in total VB 6 by about 10-fold, but had very little impact on the concentrations of the endogenous phosphorylated vitamers. Administration of either PM or PN increased their endogenous levels more than the levels of any other endogenous B 6 vitamers. PL supplementation increased the levels of plant PN and PM significantly, but not that of PL, suggesting that efficient conversion pathways from PL to PN and PM are present in tobacco. Additionally, maintenance of a stable level of PLP in the plant is not well-correlated to changes in levels of non-phosphorylated forms.

Abstract 1851: Dietary mixed tocopherols inhibit cell proliferation in mammary hyperplasia, suppress the expression of inflammatory markers, and upregulate PPARγ

Abstract Dietary intake of vitamin E, a fat-soluble vitamin, has been suggested to reduce cancer risk because of antioxidant properties. There are eight different forms of vitamin E which include four tocopherols (with a saturated phytyl tail) and four tocotrienols (with an unsaturated isoprenoid side chain) designated as α, β, γ, and Δ variants. Previous clinical and epidemiological studies on vitamin E and cancer have focused on α-tocopherol. However, γ-tocopherol has demonstrated greater anti-inflammatory and anti-tumor activity than α-tocopherol. This study assessed the potential chemopreventive activities of a tocopherol mixture containing 58% γ-tocopherol (γ-TmT) in an established rodent model of mammary carcinogenesis. Female ACI rats were utilized due to their sensitivity to 17β-estradiol to induce mammary hyperplasia and eventually mammary tumors. The rats were implanted subcutaneously with estradiol (E2) pellets containing 2.5 mg of E2 and given 0.3% or 0.5% γ-TmT in the diet for 2 or 10 weeks. Serum E2 levels were significantly reduced by the treatment with 0.5% γ-TmT. Serum levels of anti-inflammatory markers, prostaglandin E2 and 8-isoprostane, were suppressed by γ-TmT treatment. Histology of mammary glands showed evidence of epithelial hyperplasia in E2 treated rats. Immunohistochemical analysis revealed a decrease in estrogen receptor α (ERα) and proliferating cell nuclear antigen (PCNA), and an increase in cleaved-caspase3 and peroxisome proliferator-activated receptor γ (PPARγ) in the γ-TmT treated rats, indicating that tocopherol treatment inhibits cell proliferation and induces apoptosis. Treatment with γ-TmT resulted in a decrease in the expression of ERα mRNA, while ERβ and PPARγ mRNA levels were increased. These data suggest that γ-TmT inhibits the cell proliferation in mammary hyperplasia, suppresses the expression of inflammatory markers, and upregulates PPARγ. In conclusion, γ-TmT may be a promising agent for human breast cancer prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1851. doi:10.1158/1538-7445.AM2011-1851

Vitamin A Metabolism and Adipose Tissue Biology

In recent years, the importance of vitamin A in adipose tissue biology, obesity and type II diabetes has become apparent. This review focuses on recent developments within the area of vitamin A and adipose tissue biology. Adipose tissue has an active vitamin A metabolism as it not only stores vitamin A but retinol is also converted to its active metabolite retinoic acid. Several mouse models point to a relationship between vitamin A metabolism and the development of adiposity. Similarly, in vitro studies provide new molecular mechanisms for the function of different forms of vitamin A and retinol- or retinoic acid-binding proteins in adipose tissue.

Abstract 217: Vitamin E forms induce apoptosis, necrosis, and autophagy and caused accumulation of sphingolipid intermediates in human colon cancer cells

Abstract Emerging evidence by us and others suggests that certain forms of vitamin E may be promising chemoprevention agents. Here we systemically investigated the effect and mechanism of different forms of vitamin E on the growth and death of human colon cancer HT29 and HCT116 cells. γ-tocopherol (γT), δ-tocopherol (δT), and γ-tocotrienol (γTE) inhibited the proliferation of HT29 and HCT116 cells in a time- and dose-dependent manner, with the potency of γTE &amp;gt; δT &amp;gt; γT. HCT116 cells appeared to be more sensitive to the treatment than HT29 cells. Studies using annexin V and propidium iodide staining revealed that γT (50 µM) and γTE (20 µM) induced externalization of phosphatidylserine and enhanced permeability of the plasma membrane, indicating apoptosis and necrosis. On the other hand, none of the treatments activate caspase-3 and PARP except in HCT116 by γTE at 20 µM. Interestingly, γT, δT and γTE enhanced expression of microtubule-associated protein light chain-3 II (LC3 II) in both HT29 and HCT116 cells, suggesting that these vitamin E forms may induce autophagy. Consistently, electromicroscopic results showed that after 14-h treatment, γTE (20 µM) induced extensive formation of autophagic vacuoles with intact cytoplasmic membrane and little induction of chromatin condensation in HCT116. Myriocin, a specific inhibitor of serine palmitoyltransferase, a key enzyme in de novo synthesis of sphingolipids, partially protected HT29 and HCT116 cells from γTE-induced cell death. Importantly, γTE caused marked accumulation of dihydrosphingosine and dihydroceramide but not ceramide or sphingosine as early as after 8-hour incubation. Because dihydrosphingosine is shown to be a potent inducer of cell death, these findings demonstrated that vitamin E may induce apoptosis, autophagy and necrosis in colon cancer cells by modulation of sphingolipid synthesis pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 217.

Enhancement of vitamin B6 levels in seeds through metabolic engineering

As a versatile cofactor for many enzymes catalyzing important biochemical reactions, vitamin B(6) is required for all cellular organisms. In contrast to bacteria, fungi and plants, which have the ability to synthesize vitamin B(6)de novo, animals have to take up the vitamin from their diet. Plants are the major source of vitamin B(6) for animals. The recent identification of vitamin B(6) biosynthetic enzymes PDX1 and PDX2 in plants makes it possible to regulate the biosynthesis of this important vitamin. In this study, we generated Arabidopsis plants overexpressing the PDX1 and/or PDX2 gene and used a liquid chromatography/mass spectrometry/mass spectrometry method to determine the levels of different forms of vitamin B(6) in these transgenic plants. It was found that expression of the PDX genes under control of the CaMV 35S promoter caused only a limited increase in pyridoxine contents in dry seeds but not in shoots or roots. When using the Arabidopsis seed-specific 12S promoter to drive the expression of the PDX genes, the levels of vitamin B(6) increased more than twofold in transgenic plants. Our work demonstrates that it is feasible to enhance vitamin B(6) content in seeds by metabolic engineering.

Chemoprevention and vitamin E

To the Editor: As a dermatologist and certified nutrition specialist, I am delighted to see chemoprevention making its way into mainstream medical literature. The CME review by Wright et al1Wright T.I. Spencer J.M. Flowers F.P. Chemoprevention of nonmelanoma skin cancer.J Am Acad Dermatol. 2006; 54: 933-946Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar (J Am Acad Dermatol 2006;54:933-46) gives us a good introduction to the subject, but I urge the authors to reserve judgment on vitamin E. The science of vitamin E has progressed in the past 12 years since Wernighaus2Werninghaus K. Meydani M. Bhawan J. Margolis R. Blumberg J.B. Gilchrest B.A. Evaluation of the photoprotective effect of oral vitamin E supplementation.Arch Dermatol. 1994; 130: 1257-1261Crossref PubMed Scopus (129) Google Scholar published the work on which they base their rejection of its benefit. Although our limited clinical data may not support its use at this time, ongoing research suggests that our rejection may be premature. Vitamin E consists of 8 different molecules: 4 tocotrienols and 4 tocopherols. Assays based on rat fetal resorption in the 1940s identified d-alpha-tocopherol as the most biologically active form. Large doses of alpha-tocopherol can reduce red blood cell levels of D-gamma-tocopherol, the form most prevalent in our food supply.3Clarke M.W. Ward N.C. Wu J.H. Hodgson J.M. Puddey I.B. Croft K.D. 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.Am J Clin Nutr. 2006; 83: 95-102PubMed Google Scholar Recent work suggests that for some human health effects, gamma is more beneficial than alpha.4Yoshida E. Watanabe T. Takata J. Yamazaki A. Karube Y. Kobayashi S. Topical application of a novel, hydrophilic gamma-tocopherol derivative reduces photo-inflammation in mice skin.J Invest Dermatol. 2006; 126: 1633-1640Crossref PubMed Scopus (42) Google Scholar The vitamin E molecules all have right-handed stereochemistry. Synthetic alpha-tocopherol contains a racemic mixture of one active and 7 inactive molecules and, in some settings, the latter may interfere with proper function of the biologically active RRR isomer.5Blatt D.H. Pryor W.A. Mata J.E. Rodriguez-Proteau R. Re-evaluation of the relative potency of synthetic and natural alpha-tocopherol: experimental and clinical observations.J Nutr Biochem. 2004; 15: 380-395Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Mouse studies suggest that nonesterified forms of vitamin E are more effective than esterified forms.6McVean M. Liebler D.C. Prevention of DNA photodamage by vitamin E compounds and sunscreens: roles of ultraviolet absorbance and cellular uptake.Mol Carcinog. 1999; 24: 169-176Crossref PubMed Scopus (93) Google Scholar Knowing a bit about the different forms of vitamin E and how their effects differ, we can understand why we see so much variability in results from clinical trials of this nutrient. When it protects against oxidation, vitamin E itself becomes oxidized and can act as a pro-oxidant unless it is reduced, a task often performed by vitamin C.7Fuchs J. Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation.Free Radic Biol Med. 1998; 25: 1006-1012Crossref PubMed Scopus (162) Google Scholar Nutrients tend to operate as part of a system and are more effective given in combination. When designing a vitamin E study, researchers should provide vitamin C as part of the experimental protocol. Completing the cascade by also including glutathione to reconstitute vitamin C may be optimal. Our single-intervention, single-outcome research model does not readily accommodate this systems approach. The CME review authors point out that animal studies support the biochemistry of vitamin E as a chemopreventive and epidemiologic studies provide evidence that vitamin E, especially as part of a nutrient-dense diet, protects against cancer, including skin cancer. It is part of the system that evolved over the millennia to protect us against cancer. In moderate doses, in a natural mixed form, in combination with other nutrients, vitamin E has an excellent safety profile. It certainly carries far less gastrointestinal risk than another chemoprotective agent, nonsteroidal anti-inflammatory drugs. In light of an evolving understanding of vitamin E and its action, I do not think we can state that is has “been disproved” as an agent of chemoprevention.