Vitamin E Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin E, including details on benefits, dosage, supplements, antioxidants.

Liposomal formulation of alpha-tocopheryl maleamide: in vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice.

Turánek J, Wang XF, Knötigová P, Koudelka S, Dong LF, Vrublová E, Mahdavian E, Procházka L, Sangsura S, Vacek A, Salvatore BA, Neuzil J

Department of Vaccinology and Immunotherapy, Veterinary Research Institute, Brno, Czech Republic. turanek@vri.cz

The vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of alpha-tocopheryl maleamide (alpha-TAM), an esterase-resistant analogue of alpha-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of alpha-TAM towards cancer cells (MCF-7, B16F10) compared to alpha-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that alpha-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both alpha-TOS and alpha-TAM to solve the problem with cytotoxicity of free alpha-TAM (neurotoxicity and anaphylaxis), as well as the low solubility of both drugs. Remarkably, neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal alpha-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of alpha-TAM and alpha-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of alpha-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of alpha-TOS. Thus, the liposomal formulation of alpha-TAM preserved its strong anti-cancer efficacy while eliminating the in vivo toxicity found of the free drug applied in DMSO. Liposome-based targeted delivery systems for analogues of vitamin E are of interest for further development of efficient and safe drug formulations for clinical trials.

Published 1 June 2009 in Toxicol Appl Pharmacol, 237(3): 249-57.
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Articles on Vitamin E published 26 May 2009:

Aging brain: prevention of oxidative stress by vitamin E and exercise.   ScientificWorldJournal, 9: 366-72.

With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that ... [Abstract] [Full-text]

Articles on Vitamin E published 21 May 2009:

Vitamin E reverses impaired linker for activation of T cells activation in T cells from aged C57BL/6 mice.   J Nutr, 139(6): 1192-7.

Supplemental vitamin E alleviates age-related defects in interleukin (IL)-2 production, T cell proliferation, and immune synapse formation. Here, we evaluated the effect of in vitro supplementation with 46 mumol/L of vitamin E on T cell receptor-proximal signaling events of CD4(+) T cells from young (4-6 mo) and old (22-26 mo) C57BL mice. Aged murine CD4(+) T cells stimulated via CD3 and CD28, tyrosine 191 of the adaptor protein Linker for Activation of T cells (LAT), was hypo-phosphorylated. ... [Abstract] [Full-text]

Dietary beta-tocopherol and linoleic acid, serum insulin, and waist circumference predict circulating sex hormone-binding globulin in premenopausal women.   J Nutr, 139(6): 1135-42.

Reduced levels of circulating sex hormone-binding globulin (SHBG) are implicated in the etiology of sex steroid-related pathologies and the metabolic syndrome. Dietary correlates of serum SHBG remain unclear and were studied in a convenient cross-sectional sample of healthy 30- to 40-y-old women (n = 255). By univariate analyses, serum SHBG correlated negatively with several indices of the metabolic syndrome, such as BMI, waist circumference, hip circumference (r = -0.36 to -0.44; P < ... [Abstract] [Full-text]

Multivitamin use and telomere length in women.   Am J Clin Nutr, 89(6): 1857-63.

BACKGROUND: Telomere length may be a marker of biological aging. Multivitamin supplements represent a major source of micronutrients, which may affect telomere length by modulating oxidative stress and chronic inflammation. OBJECTIVE: The objective was to examine whether multivitamin use is associated with longer telomeres in women. DESIGN: We performed a cross-sectional analysis of data from 586 early participants (age 35-74 y) in the Sister Study. Multivitamin use and nutrient intakes were ... [Abstract] [Full-text]

Articles on Vitamin E published 7 May 2009:

Malathion-induced oxidative stress in human erythrocytes and the protective effect of vitamins C and E in vitro.   Environ Toxicol, 24(3): 235-42.

Malathion is an organophosphate (OP) pesticide that has been shown to induce oxidative stress in erythrocytes through the generation of free radicals and alteration of the cellular antioxidant defense system. We examined the effect of several different doses of malathion (25, 75, 200 microM), or malathion in combination with vitamin C (VC; 10 microM) or vitamin E (VE; 30 microM), on the levels of malondialdehyde (MDA), and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase ... [Abstract] [Full-text]

Articles on Vitamin E published 29 April 2009:

Protein tyrosine phosphorylation under capacitating conditions in porcine fresh spermatozoa and sperm cryopreserved with and without alpha tocopherol.   Andrologia, 41(3): 184-92.

The aim of this study was to evaluate the capacitation behaviour of fresh and alpha-tocopherol frozen spermatozoa. Spermatozoa frozen with or without alpha-tocopherol and fresh semen were incubated under capacitating conditions. Aliquots were collected at 0, 15, 30, 45, 60, 90, 120 and 180 min of incubation time. Parameters of semen quality were evaluated by optical microscopy and capacitation was determined by the epifluorescence chlortetracycline technique. Protein tyrosine phosphorylation ... [Abstract] [Full-text]

Articles on Vitamin E published 28 April 2009:

A redox-silent analogue of tocotrienol acts as a potential cytotoxic agent against human mesothelioma cells.   Life Sci, 84(19): 650-6.

AIMS: Malignant mesothelioma is an aggressive cancer with no effective treatment options. A redox-silent analogue of alpha-tocotrienol, 6-O-carboxypropyl-alpha-tocotrienol (T3E) is a new potential anti-carcinogenic agent with less toxic effect on non-tumorigenic cells. Here, we evaluated the effect of T3E on killing of chemoresistant mesothelioma cell (H28). MAIN METHODS: The cytotoxic effect of T3E was evaluated by a WST-1 assay, and cell cycle and apoptosis analysis were done by FACS. Each ... [Abstract] [Full-text]

Articles on Vitamin E published 24 April 2009:

d-Dlta-tocotrienol-mediated suppression of the proliferation of human PANC-1, MIA PaCa-2, and BxPC-3 pancreatic carcinoma cells.   Pancreas, 38(4): e124-36.

OBJECTIVE: The rate-limiting activity of the mevalonate pathway, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, provides intermediates essential for growth. Competitive inhibitors of HMG CoA reductase, such as the statins, and down-regulators of reductase, such as the tocotrienols, suppress tumor growth. We evaluated the impact of d-delta-tocotrienol, the most potent vitamin E isomer, on human MIA PaCa-2 and PANC-1 pancreatic carcinoma cells and BxPC-3 pancreatic ductal ... [Abstract] [Full-text]

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