Acute effects of a single dose of tocotrienols on insulinemic and inflammatory responses in metabolic syndrome subjects after a high-fat challenge.

BACKGROUND/OBJECTIVES: Evidence shows that tocotrienols potentially reverse various chronic disease progressions caused by the metabolic syndrome. We aimed to investigate the acute effects of a single-dose supplementation of gamma and delta tocotrienols (γδ-T3, 1:4 ratio) compared with those in placebo on the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects. SUBJECTS/METHODS: Thirty metabolic syndrome subjects (15 men and 15 women) were recruited to a randomized, double-blinded and crossover study. The subjects were administered a single dose of 200 mg or 400 mg γδ-T3 emulsions or placebo incorporated into a glass of strawberry-flavored milkshake, consumed together with a high-fat muffin. Blood samples were collected at 0, 5, 15, 30, 60, 90, 120, 180, 240, 300 and 360 min after meal intake. RESULTS: Plasma vitamin E levels reflected the absorption of γδ-T3 after treatments. Postprandial changes in serum C-peptide, serum insulin, plasma glucose, triacylglycerol, non-esterified fatty acid and adiponectin did not differ between treatments, with women displaying delayed increase in the aforementioned markers. No significant difference between treatments was observed for plasma cytokines (interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha) and thrombogenic markers (plasminogen activator inhibitor type 1 and D-dimer). CONCLUSIONS: Supplementation of a single dose of γδ-T3 did not change the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects.

Virgin olive oil, palm olein and coconut oil diets do not raise cell adhesion molecules and thrombogenicity indices in healthy Malaysian adults.

BACKGROUND/OBJECTIVES: Effects of high-protein diets that are rich in saturated fats on cell adhesion molecules, thrombogenicity and other nonlipid markers of atherosclerosis in humans have not been firmly established. We aim to investigate the effects of high-protein Malaysian diets prepared separately with virgin olive oil (OO), palm olein (PO) and coconut oil (CO) on cell adhesion molecules, lipid inflammatory mediators and thromobogenicity indices in healthy adults. METHODS: A randomized cross-over intervention with three dietary sequences, using virgin OO, PO and CO as test fats, was carried out for 5 weeks on each group consisting of 45 men and women. These test fats were incorporated separately at two-thirds of 30% fat calories into high-protein Malaysian diets. RESULTS: For fasting and nonfasting blood samples, no significant differences were observed on the effects of the three test-fat diets on thrombaxane B2 (TXB2), TXB2/PGF1α ratios and soluble intracellular and vascular cell adhesion molecules. The OO diet induced significantly lower (P<0.05) plasma leukotriene B4 (LTB4) compared with the other two test diets, whereas PGF1α concentrations were significantly higher (P<0.05) at the end of the PO diet compared with the OO diet. CONCLUSION: Diets rich in saturated fatty acids from either PO or CO and high in monounsaturated oleic acid from virgin OO do not alter the thrombogenicity indices-cellular adhesion molecules, thromboxane B2 (TXB2) and TXB2/prostacyclin (PGF1α) ratios. However, the OO diet lowered plasma proinflammatory LTB4, whereas the PO diet raised the antiaggregatory plasma PGF1α in healthy Malaysian adults. This trial was registered at clinicaltrials.gov as NCT 00941837.

Tocotrienols promote apoptosis in human breast cancer cells by inducing poly(ADP-ribose) polymerase cleavage and inhibiting nuclear factor kappa-B activity.

OBJECTIVES: Tocotrienols and tocopherols are members of the vitamin E family, with similar structures; however, only tocotrienols have been reported to achieve potent anti-cancer effects. The study described here has evaluated anti-cancer activity of vitamin E to elucidate mechanisms of cell death, using human breast cancer cells. MATERIALS AND METHODS: Anti-cancer activity of a tocotrienol-rich fraction (TRF) and a tocotrienol-enriched fraction (TEF) isolated from palm oil, as well as pure vitamin E analogues (α-tocopherol, α-, δ- and γ-tocotrienols) were studied using highly aggressive triple negative MDA-MB-231 cells and oestrogen-dependent MCF-7 cells, both of human breast cancer cell lines. Cell population growth was evaluated using a Coulter particle counter. Cell death mechanism, poly(ADP-ribose) polymerase cleavage and levels of NF-κB were determined using commercial ELISA kits. RESULTS: Tocotrienols exerted potent anti-proliferative effects on both types of cell by inducing apoptosis, the underlying mechanism of cell death being ascertained using respective IC50 concentrations of all test compounds. There was marked induction of apoptosis in both cell lines by tocotrienols compared to treatment with Paclitaxel, which was used as positive control. This activity was found to be associated with cleavage of poly(ADP-ribose) polymerase (a DNA repair protein), demonstrating involvement of the apoptotic cell death signalling pathway. Tocotrienols also inhibited expression of nuclear factor kappa-B (NF-κB), which in turn can increase sensitivity of cancer cells to apoptosis. CONCLUSION: Tocotrienols induced anti-proliferative and apoptotic effects in association with DNA fragmentation, poly(ADP-ribose) polymerase cleavage and NF-κB inhibition in the two human breast cancer cell lines.

Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers.

BACKGROUND/OBJECTIVES: Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems. The objective of this study was to assess the effects of tocotrienol-rich fraction (TRF) supplementation on immune response following tetanus toxoid (TT) vaccine challenge in healthy female volunteers. SUBJECTS/METHODS: In this double-blinded, placebo-controlled clinical trial, participants were randomly assigned to receive either placebo (control group) or 400 mg of TRF (study group) supplementation daily. Over the 2-month period of the study, volunteers were asked to attend three clinical sessions (that is, on days 0, 28 and 56) and blood samples were obtained from the volunteers during the follow-up. On day 28, all volunteers were also vaccinated with the TT vaccine (20 Lf) intramuscularly. RESULTS: The results from the clinical trial showed that TRF supplementation significantly increased the total vitamin E level in the plasma of the TRF-supplemented volunteers compared with the placebo group, indicating overall compliance. Volunteers supplemented with TRF showed a significantly (P < 0.05) enhanced production of interferon-γ and interleukin (IL)-4 by the mitogen or TT-stimulated leukocytes compared with the control group. Volunteers from the TRF group produced significantly (P < 0.05) lower amounts of IL-6 compared with the placebo group. Anti-TT IgG production was also significantly (P < 0.05) augmented in the TRF-supplemented group compared with the placebo group. CONCLUSIONS: We conclude that TRF has immunostimulatory effects and potential clinical benefits to enhance immune response to vaccines.

Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion.

AIM: Present study aimed to elucidate the suppression of serum lipids by gamma- and delta-tocotrienol (γδT3). METHODS: The lipid-lowering effects of γδT3 were investigated using HepG2 liver cell line, hypercholesterolemic mice and borderline-high cholesterol patients. RESULTS: In-vitro results demonstrated two modes of action. First, γδT3 suppressed the upstream regulators of lipid homeostasis genes (DGAT2, APOB100, SREBP1/2 and HMGCR) leading to the suppression of triglycerides, cholesterol and VLDL biosyntheses. Second, γδT3 enhanced LDL efflux through induction of LDL receptor (LDLr) expression. Treatment of LDLr-deficient mice with 1 mg/day (50 mg/kg/day) γδT3 for one-month showed 28%, 19% reduction in cholesterol and triglyceride levels respectively, whereas HDL level was unaltered. The lipid-lowering effects were not affected by alpha-tocopherol (αTP). In a placebo-controlled human trial using 120 mg/day γδT3, only serum triglycerides were lowered by 28% followed by concomitant reduction in the triglyceride-rich VLDL and chylomicrons. In contrast, total cholesterol, LDL and HDL remained unchanged in treated and placebo groups. The discrepancies between in-vitro, in-vivo and human studies may be attributed to the differential rates of post-absorptive γδT3 degradation and LDL metabolism. CONCLUSION: Reduction in triglycerides synthesis and transport may be the primary benefit caused by ingesting γδT3 in human.

Health promoting effects of phytonutrients found in palm oil.

The oil palm tree, Elaeis guineesis, is the source of palm oil, otherwise known as the "tropical golden oil". To date, Malaysia and Indonesia are the leading producers of palm oil. Palm oil is widely used for domestic cooking in Malaysia. Palm oil is a rich source of phytonutrients such as tocotrienols, tocopherol, carotene, phytosterols, squalene, coenzyme Q10, polyphenols, and phospholipids. Although the phytonutrients constitute only about 1% of its weight in crude palm oil, these are the main constituents through which palm oil exhibits its nutritional properties. Among the major health promoting properties shown to be associated with the various types of phytonutrients present in palm oil are anti-cancer, cardio-protection and anti-angiogenesis, cholesterol inhibition, brain development and neuro protective properties, antioxidative defence mechanisms, provitamin A activity and anti-diabetes.

Antioxidantes y cáncer de próstata / Antioxidants and prostate cancer

La próstata es la glándula que produce semen (el fluido que lleva esperma) y es esencial para la reproducción. El cáncer que se inicia en la próstata se conoce como cáncer de próstata primario (o cáncer prostático) y puede extenderse a distintos órganos. Se considera como la segunda causa de muerte de hombres en el mundo. La etiología del cáncer de próstata es aún bastante desconocida, pero se tiende mucho a creer que se relaciona con la acción estimulante de la testosterona. La mayoría de los casos de cáncer tienen un período de latencia de 10 a 20 años, lo que permite un amplio margen para tomar medidas preventivas. Los tocoferoles y tocotrienoles son compuestos muy conocidos por sus propiedades antioxidantes como inhibidores de los radicales libres y tienen el potencial necesario para disminuir el daño al ADN, inhibir la transformación maligna e inducir la apoptosis. La mayor abundancia de tocoferoles se presenta en los aceites extraídos de la soya, y de la semillas de algodón y girasol, mientras que los tocotrienoles se encuentran principalmente en el aceite de palma y en fracciones de aceite de cereales tales como trigo, cebada y arroz. La posible prevención de este tipo de cáncer a través de factores relacionados con la dieta resulta en realidad muy digna de atención.

The prostate is the gland taht produces semen (the fluid that carries sperm) and it is essential for reproduction. Cancer that begins in the prostate is called primary prostate cancer (or prostatic cancer) and it may spread to different organs. It is considered as the second leading cause of cancer-related death in men worldwide. The etiology of prostate cancer remains largely unknown, but it is widely believed to be related to the stimulating action of testosterone. Most cancer cases have a latency period of 10 to 20 years, which provides ample time for preventive measures. Tocopherols and tocotrienols are compounds well-known for their antioxidant properties as free radical scavengers an...

Effect of a carotene concentrate on the growth of human breast cancer cells and pS2 gene expression.

Breast cancer is the most common cancer in women worldwide. The growth of breast cancer cells is either hormone-dependent or hormone-independent. Both types are represented in vitro by the estrogen-receptor positive (ER+) MCF-7 and the estrogen-receptor negative (ER-) MDA-MB-231 cell lines, respectively. The pS2 gene is an estrogen-regulated gene and serves as a marker for the ER+ tumours. Carotenoids are pigments with anti-cancer properties besides having pro-vitamin A, antioxidant and free-radical quenching effects. This study was designed firstly, to compare the effect of palm oil carotene concentrate with retinoic acid on the growth of the ER+ MCF-7 and the ER- MDA-MB-231 cells; and secondly to evaluate the effect of the palm oil carotene concentrate on the regulation of pS2 mRNA. The growth experiments were performed with monolayer cells seeded in phenol red free RPMI 1640 culture media and subsequently treated with varying concentrations of either retinoic acid or palm oil carotenoids. The cell numbers were determined at the start of each experiment and then at successive time intervals. The results showed that the palm oil carotene concentrate caused dose-dependent inhibition of estradiol-stimulated growth of MCF-7 cells but did not affect the proliferation of MDA-MB-231 cells. Retinoic acid caused similar, albeit more potent effects, as significant inhibition was observed at lower concentrations than the palm oil carotenoids. In the pS2 gene expression experiment, cell monolayers were treated with the carotene concentrate (10(-6) M), either with or without supplemented estradiol (10(-8) M), and subsequently the RNA was extracted. Northern blotting was performed and the regulation of pS2 mRNA determined using a 32P-labelled pS2 cDNA probe. The results showed that the palm oil carotene concentrate did not affect the expression of pS2 mRNA and are therefore independent of the estrogen-regulated pathway.

Effect of retinoic acid and palm oil carotenoids on oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase activities in MCF-7 and MDA-MB-231 breast cancer cell lines.

Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.

Tocotrienols inhibit growth of ZR-75-1 breast cancer cells.

The vitamin E component of palm oil provides a rich source of tocotrienols which have been shown previously to be growth inhibitory to two human breast cancer cell lines: responsive MCF7 cells and unresponsive MDA-MB-231 cells. Data presented here shows that the tocotrienol-rich fraction (TRF) of palm oil and individual fractions (alpha, gamma and delta) can also inhibit the growth of another responsive human breast cancer cell line, ZR-75-1. At low concentrations in the absence of oestrogen tocotrienols stimulated growth of the ZR-75-1 cells, but at higher concentrations in the presence as well as in the absence of oestradiol, tocotrienols inhibited cell growth strongly. As for MCF7 cells, alpha-tocopherol had no effect on growth of the ZR-75-1 cells in either the absence or presence of oestradiol. In studying the effects of tocotrienols in combination with antioestrogens, it was found that TRF could further inhibit growth of ZR-75-1 cells in the presence of tamoxifen (10(-7) M and 10(-8) M). Individual tocotrienol fractions (alpha, gamma, delta) could inhibit growth of ZR-75-1 cells in the presence of 10(-8) M oestradiol and 10(-8) M pure antioestrogen ICI 164,384. The immature mouse uterine weight bioassay confirmed that TRF could not exert oestrogen antagonist action in vivo. These results provide evidence of wider growth-inhibitory effects of tocotrienols beyond MCF7 and MDA-MB-231 cells, and with an oestrogen-independent mechanism of action, suggest a possible clinical advantage in combining administration of tocotrienols with antioestrogen therapy.

Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status.

Potential antiproliferative effects of tocotrienols, the major vitamin E component in palm oil, were investigated on the growth of both estrogen-responsive (ER+) MCF7 human breast cancer cells and estrogen-unresponsive (ER-) MDA-MB-231 human breast cancer cells, and effects were compared with those of alpha-tocopherol (alphaT). The tocotrienol-rich fraction (TRF) of palm oil inhibited growth of MCF7 cells in both the presence and absence of estradiol with a nonlinear dose-response but such that complete suppression of growth was achieved at 8 microg/mL. MDA-MB-231 cells were also inhibited by TRF but with a linear dose-response such that 20 microg/mL TRF was needed for complete growth suppression. Separation of the TRF into individual tocotrienols revealed that all fractions could inhibit growth of both ER+ and ER- cells and of ER+ cells in both the presence and absence of estradiol. However, the gamma- and delta-fractions were the most inhibitory. Complete inhibition of MCF7 cell growth was achieved at 6 microg/mL of gamma-tocotrienol/delta-tocotrienol (gammaT3/deltaT3) in the absence of estradiol and 10 microg/mL of deltaT3 in the presence of estradiol, whereas complete suppression of MDA-MB-231 cell growth was not achieved even at concentrations of 10 microg/mL of deltaT3. By contrast to these inhibitory effects of tocotrienols, alphaT had no inhibitory effect on MCF7 cell growth in either the presence or the absence of estradiol, nor on MDA-MB-231 cell growth. These results confirm studies using other sublines of human breast cancer cells and demonstrate that tocotrienols can exert direct inhibitory effects on the growth of breast cancer cells. In searching for the mechanism of inhibition, studies of the effects of TRF on estrogen-regulated pS2 gene expression in MCF7 cells showed that tocotrienols do not act via an estrogen receptor-mediated pathway and must therefore act differently from estrogen antagonists. Furthermore, tocotrienols did not increase levels of growth-inhibitory insulin-like growth factor binding proteins (IGFBP) in MCF7 cells, implying also a different mechanism from that proposed for retinoic acid inhibition of estrogen-responsive breast cancer cell growth. Inhibition of the growth of breast cancer cells by tocotrienols could have important clinical implications not only because tocotrienols are able to inhibit the growth of both ER+ and ER- phenotypes but also because ER+ cells could be growth-inhibited in the presence as well as in the absence of estradiol. Future clinical applications of TRF could come from potential growth suppression of ER+ breast cancer cells otherwise resistant to growth inhibition by antiestrogens and retinoic acid.

3,3',4,4'-tetrachlorobiphenyl (TCB) can enhance DMBA-induced mammary carcinogenesis in the rat.

Polychlorinated biphenyls (PCBs) are fat-soluble environmental pollutants which can be stored in the fatty tissue of breast and secreted in milk. Previous studies have shown that PCBs can influence liver carcinogenesis in animal models but no such studies have been reported in breast. These experiments aimed to determine whether a PCB congener could influence mammary carcinogenesis using the rat DMBA-induced mammary tumour model system. 3,3',4,4'-Tetrachlorobiphenyl (TCB) enhanced the development of DMBA-induced mammary tumours in young female rats and did so in animals fed either a low-fat (5% w/w corn oil) or a high-fat (20% w/w corn oil) diet. The combination of TCB and high-fat diet resulted in tumours growing so fast that the experiment had to be terminated at 10.5 weeks for humane reasons. At termination the total numbers of tumours in each group of 20 rats were: 4 in the low-fat group, 22 in the low-fat plus TCB group, 25 in the high-fat group and 50 in the high-fat plus TCB group. Histopathological analysis confirmed that 98% of the tumours were mammary carcinomas, predominantly in situ ductal carcinomas, but, in addition, revealed that 13 of the tumours had an invasive phenotype of which 12/13 had all arisen in TCB-treated animals. This demonstrates, for the first time, that a PCB congener can influence mammary carcinogenesis.

3,5,3',5'-tetrachlorobiphenyl is a weak oestrogen agonist in vitro and in vivo.

Polychlorinated biphenyls (PCBs) are widespread, persistent environmental contaminants of which some congeners can act as endocrine disrupters. Previous work has shown that 3,4,3',4'-tetrachlorobiphenyl (PCB77) can act as an oestrogen with actions mediated through the oestrogen receptor. Here, oestrogenic actions have been assessed for two further tetrachlorobiphenyl isomers. Assays of oestrogenic action have involved (1) ligand regulation of oestrogen-sensitive gene expression; (2) ligand regulation of cell growth in oestrogen-dependent human breast cancer cell lines MCF7 McGrath and ZR-75-1; and (3) ligand activity in the immature mouse uterine weight bioassay in vivo. These results demonstrate that 3,5,3',5'-tetrachlorobiphenyl (PCB 80) can be considered to be a weak oestrogen agonist, but the 2,5,2',5'-congener (PCB 52) revealed no oestrogenic properties in any of these assays. Implications of these results are discussed in relation to structure-activity predictions for environmental oestrogens.

Tocotrienols from palm oil as effective inhibitors of protein oxidation and lipid peroxidation in rat liver microsomes.

Tocotrienols from palm oil showed significant ability to inhibit oxidative damage induced by ascorbate-Fe2+ and photosensitization, involving different mechanisms, in rat liver microsomes. The tocotrienol-rich fraction from palm oil (TRF), being tried as a more economical and efficient substitute for alpha-tocopherol, showed time- and concentration-dependent inhibition of protein oxidation as well as lipid peroxidation. It was more effective against protein oxidation. The extent of inhibition by TRF varied with different peroxidation products such as conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS). Among the constituents of TRF, gamma-tocotrienol was the most effective followed by its alpha- and delta-isomers. In general, at a low concentration of 5 microM, TRF was able to prevent oxidative damage to significant extent (37% inhibition of protein oxidation and 27-30% of lipid peroxidation at 1 h of incubation). The protective ability of TRF (30.1% at 5 microM with TBARS formation) was significantly higher than that of the dominant form of vitamin E, alpha-tocopherol (16.5% under same conditions). Hence our studies indicate that this fraction from palm oil can be considered as an effective natural antioxidant supplement capable of protecting cellular membranes against oxidative damage.

3,4,3',4'-Tetrachlorobiphenyl acts as an estrogen in vitro and in vivo.

Polychlorinated biphenyls (PCBs) are one of the most widespread, persistent man-made products in the ecosystem giving rise to serious environmental contamination and potential hazard to health. The PCBs, in common with other compounds such as the dioxins, have been shown to exert some biological actions mediated through the aryl hydrocarbon receptor. Evidence for interaction of PCBs with other nuclear receptors has been sparse. Here we present evidence that 3,4,3',4'-tetrachlorobiphenyl (TCB) (PCB77), a PCB with high toxicity and significant bioaccumulation, can act as an estrogen with actions mediated through the estrogen receptor. Evidence is presented from multiple assay systems including 1) ligand binding to estrogen receptor in a competitive binding assay, 2) ligand ability to induce estrogen receptor binding to DNA, 3) ligand regulation of gene expression from a transfected exogenous (ERE-tk-CAT) or an endogenous (pS2) estrogen-regulated gene, 4) ligand regulation of cell growth in estrogen-dependent human breast cancer cell lines MCF7 and ZR-75-1, and 5) ligand activity in the immature mouse uterine weight bioassay in vivo. These results demonstrate that TCB (PCB77) can be included in the increasing list of environmental pollutants that possess the ability to mimic estrogen action and be termed an environmental estrogen. Since the concentrations of TCB used here (10(-9) M; 292 ng/liter) are not incompatible with levels of PCB/TCB found in human tissues, these results may have physiological relevance. Use of multiple approaches to study estrogenic action demonstrates that one congener can act as both an agonist and antagonist of estrogen action and that the magnitude of these effects can alter according to the molecular environment.

Effect of tocotrienols on the growth of a human breast cancer cell line in culture.

The tocotrienol-rich fraction (TRF) of palm oil consists of tocotrienols and some alpha-tocopherol (alpha-T). Tocotrienols are a form of vitamin E having an unsaturated side-chain, rather than the saturated side-chain of the more common tocopherols. Because palm oil has been shown not to promote chemically-induced mammary carcinogenesis, we tested effects of TRF and alpha-T on the proliferation, growth, and plating efficiency (PE) of the MDA-MB-435 estrogen-receptor-negative human breast cancer cells. TRF inhibited the proliferation of these cells with a concentration required to inhibit cell proliferation by 50% of 180 microgram/mL whereas alpha-T had no effect at concentrations up to 1000 microgram/mL as measured by incorporation of [3H]thymidine. The effects of TRF and alpha-T also were tested in longer-term growth experiments, using concentrations of 180 and 500 microgram/mL. We found that TRF inhibited the growth of these cells by 50%, whereas alpha-T did not. Their effect on the ability of these cells to form colonies also was studied, and it was found that TRF inhibited PE, whereas alpha T had no effect. These results suggest that the inhibition is due to the presence of tocotrienols in TRF rather than alpha T.

Influence of palm oil or its tocotrienol-rich fraction on the lipid peroxidation potential of rat liver mitochondria and microsomes.

The effect of palm oil, a widely used vegetable oil, rich in tocotrienols, on peroxidation potential of rat liver was examined. Long-term feeding of rats with palm oil as one of the dietary components significantly reduced the peroxidation potential of hepatic mitochondria and microsomes. As compared to hepatic mitochondria isolated from rats fed control or corn oil-rich diet, those from palm oil-fed group showed significantly less susceptibility to peroxidation induced by ascorbate and NADPH. However, in microsomes, only NADPH-induced lipid peroxidation was significantly reduced in rats fed palm oil rich-diet. Though the accumulation of thiobarbituric acid reactive substances during ascorbate-induced lipid peroxidation in mitochondria from rats fed corn oil-rich diet supplemented with tocotrienol-rich fraction (TRF) of palm oil was similar to that of control rats, the initial rate of peroxidation was much slower than those from control or corn oil fed diets. Our in vitro studies as well as analyses of co-factors related to peroxidation potential indicated that the observed decrease in palm oil-fed rats may be due to increased amount of antioxidants in terms of tocotrienol as well as decrease in the availability of substrates for peroxidation.