Blog Archives

Gamma-tocotrienol reverses multidrug resistance of breast cancer cells with a mechanism distinct from that of atorvastatin.

Ding Y, Peng Y, Deng L, Fan J, Huang B.

J Steroid Biochem Mol Biol. 2017 Mar;167:67-77. doi: 10.1016/j.jsbmb.2016.11.009. Epub 2016 Nov 15.

Abstract

In addition to its antioxidant properties, γ-tocotrienol also has the ability to inhibit HMG-CoA reductase, which is the key enzyme in the mevalonate pathway for cholesterol biosynthesis. Statins, the competitive inhibitors of HMG-CoA reductase, display potent anticancer activity and reversal ability of multidrug resistance in a variety of tumor cells, which is believed to be due to their inhibition of HMG-CoA reductase. Here, we determined the role of the mevalonate pathway in γ-tocotrienol-mediated reversal of multidrug resistance in cancer cells. We found both γ-tocotrienol and atorvastatin effectively reversed multidrug resistance of MCF-7/Adr and markedly inhibited the intracellular levels of FPP and GGPP. Exogenous addition of mevalonate or FPP and GGPP almost completely prevented the reversal ability of atorvastatin but only partly attenuated the reversal effect of γ-tocotrienol on doxorubicin resistance. In addition, γ-tocotrienol actively inhibited the expression of P-gp and increased the accumulation of doxorubicin in cells, which led to the enhanced G2/M arrest and cell apoptosis. Taken together, γ-tocotrienol reversed the multidrug resistance of MCF-7/Adr with a mechanism distinct from that of atorvastatin. Instead of the mevalonate pathway, the inhibition of P-gp expression is a potential mechanism by which γ-tocotrienol reverses multidrug resistance in MCF-7/Adr.

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α-Tocopherol as functional excipient for resveratrol and coenzyme Q10-loaded SNEDDS for improved bioavailability and prophylaxis of breast cancer.

Jain S, Garg T, Kushwah V, Thanki K, Agrawal AK, Dora CP.

J Drug Target. 2017 Mar 8:1-12. doi: 10.1080/1061186X.2017.1298603. [Epub ahead of print]

Abstract

The present study evaluates the prophylactic efficacy of α-tocopherol (α-TOH), resveratrol (RES), and coenzyme Q10 (CoQ10) co-loaded self-nanoemulsifying drug delivery system (α-TOH-RES-CoQ10 SNEDDS) in 7,12-Dimethylbenz[a]anthracene (DMBA) induced breast cancer model. SNEDDS formulation components were rationally selected and optimized for maximum drug loading by applying the design of experiments and further evaluated for stability in simulated gastrointestinal fluids, functional stability of antioxidants, in vitro release, Caco-2 cell uptake, oral bioavailability and prophylactic anticancer activity. The SNEDDS demonstrated excellent stability in stimulated gastrointestinal fluids. The functional activity of antioxidants was confirmed by 2,2-diphenylpicrylhydrazyl (DPPH) scavenging assay wherein significantly (p > .05) higher antioxidant activity was observed in case of SNEDDS as compared with free antioxidants. Coumarin 6 (C-6)-loaded SNEDDS formulation demonstrated remarkably higher Caco-2 cell uptake in comparison with free C-6, indicative of efficient internalization of sub-micron SNEDDS droplets by Caco-2 cells. In line with Caco-2 cell uptake observations, α-TOH-RES-CoQ10-SNEDDS showed ∼2.30- and ∼3.64-fold increase in the AUC0-∞ values of RES and CoQ10 in comparison with free antioxidants. Significantly lower (p < .001) tumor volume (∼327 mm3) was found in case of animals treated with α-TOH-RES-CoQ10-SNEDDS in comparison with free antioxidant combination (∼1070 mm3) and DMBA control (∼1540 mm3) groups. Conclusively, the proposed strategy posed great potential in improving the prophylactic activity of antioxidants and hold promise for further exploration.

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Inhibitory effect of a redox-silent analogue of tocotrienol on hypoxia adaptation in prostate cancer cells.

Shiozawa N, Sugahara R, Namiki K, Sato C, Ando A, Sato A, Virgona N, Yano T.

Anticancer Drugs. 2017 Mar;28(3):289-297. doi: 10.1097/CAD.0000000000000460.

Abstract

Prostate cancer (PCa) is one of the most common cancers in Western countries and acquires a malignant phenotype, androgen-independent growth. PCa under hypoxia often has resistance to chemotherapy and radiotherapy. However, an effective therapy against PCa under hypoxia has not yet been established. In this report, we investigated the inhibitory effect of a redox-silent analogue of tocotrienol on the survival of a human androgen-independent PCa cell line (PC3) under hypoxia. We found that the redox-silent analogue exerted a cytotoxic effect on PC3 cells in a dose-dependent manner irrespective of either hypoxia or normoxia. Moreover, under hypoxia, the analogue dose dependently reduced the protein levels of hypoxia-inducible factor (HIF)-1α and HIF-2α. In addition, a specific inhibitor toward HIF-1α induced cytotoxicity on PC3 cells, whereas selective inhibition of HIF-2α exerted no effect. Furthermore, suppression of HIFs levels by the analogue in hypoxic PC3 cells was closely associated with the inactivation of Fyn, a member of the nonreceptor tyrosine kinase family, as confirmed by the action of a specific inhibitor toward the kinase (PP2). Taken together, these results suggest that the tocotrienol analogue could inhibit the survival of PC3 cells under hypoxia, mainly by the inhibition of Fyn/HIF-1α signaling, and this may lead to the establishment of a new effective therapy for androgen-independent PCa.

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The secret to baking healthier bread is vitamin E-rich palm oil

If you’re a baker, you may be interested in this fool-proof way to bake healthier bread. An Australian food scientist suggests using palm oil instead soybean or canola oil. Unlike those other oils, Malaysian sustainable palm oil is chock full of nutrients, and won’t break down at high temperatures. Oliver Buddrick, Ph.D., is not your ordinary scientist. He’s also a master pastry chef, and is studying ways to enhance baked goods’ health benefits. His recent Journal of Food Chemistry report details the benefits of using red palm oil when baking.

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Vitamin E for the treatment of children with hepatitis B e antigen-positive chronic hepatitis: A systematic review and meta-analysis.

Fiorino S, Bacchi-Reggiani ML, Leandri P, Loggi E, Andreone P.

World J Hepatol. 2017 Feb 28;9(6):333-342. doi: 10.4254/wjh.v9.i6.333.

Abstract

To assess vitamin E efficacy, defined as its ability to induce hepatitis B e antigen (HBeAg) seroconversion, in children with HBeAg-positive persistent hepatitis. In July 2016, we extracted articles published in MEDLINE and the Cochrane Library using the following search terms: “chronic hepatitis B”, “children”, “childhood”, “therapy”, “treatment”, “vitamin E”, “tocopherols”, “tocotrienols“. Only randomized controlled trials (RCTs) published in English language were collected. Three RCTs met inclusion criteria and were considered in the present meta-analysis. Overall, 23/122 children in the treatment group underwent HBeAg seroconversion vs 3/74 in the control group (OR = 3.96, 95%CI: 1.18-13.25, P = 0.025). Although our meta-analysis has several limits, including the very small number of available studies and enrolled children with HBeAg positivity-related hepatitis, it suggests that vitamin E use may enhance the probability to induce HBeAg seroconversion in these patients. Further well designed and adequately sized trials are required to confirm or deny these very preliminary results.

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Nature’s Best Kept Secret – Vitamin E Tocotrienols

Tocotrienol, a member of vitamin E family. The natural vitamin E family comprises four tocopherol and four tocotrienol isomers, namely alpha (α), beta (β), gamma (γ) and delta (δ). Throughout the past 30 years, very few vitamin E studies focused on tocotrienols although tocotrienols constitute half of the entire vitamin E family. In recent years, tocotrienol research has gained much prominence due to its potential health attributes. Tocotrienols are not only structurally different from tocopherols, but also possess biological functions which are not shared by the tocopherol isomers.

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Researchers find new clues about why we may want to add more Vitamin E tocotrienols to our diets

Researchers in Malaysia have uncovered another reason why you may want to start eating more foods rich in Vitamin E tocotrienols. In a new study published in the January 2012 issue of Nutrition Journal, it was revealed that these super healthy nutrients are more difficult for our bodies to absorb than other more common forms of Vitamin E, and that they appear to be metabolized (used up) faster.

The good news is that you may only need a tiny amount of tocotrienols in your body to get their neuroprotective benefits, and adding them to your diet is easier than ever.

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Antioxidant effect of vitamin E and 5-aminosalicylic acid on acrylamide induced kidney injury in rats.

Rajeh NA, Al-Dhaheri NM.

Saudi Med J. 2017 Feb;38(2):132-137. doi: 10.15537/smj.2017.2.16049.

Abstract

OBJECTIVES:

To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone). After 5 days of ACR oral gavage treatment, the rats were observed for 24 hours then killed. Histopathology for the kidney and lactate dehydrogenase assay were carried out.  Results: Acrylamide produced significant pathological changes in the kidney with acute tubular necrosis in the distal tubules that could be reversed by concomitant injection of rat with 5-ASA. Together with vitamin E, 5-ASA, showed maximum renal protection. No statistically significant difference was observed in either body weights or lactate dehydrogenase activity of ACR treated rats.  Conclusion: Acrylamide exposure leads to adverse clinical pathologies of renal tubules, which were reversed by a concomitant treatment with 5-ASA and vitamin-E.

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γ-Tocotrienol prevents cell cycle arrest in aged human fibroblast cells through p16INK4a pathway.

Zainuddin A, Chua KH, Tan JK, Jaafar F, Makpol S.

J Physiol Biochem. 2017 Feb;73(1):59-65. doi: 10.1007/s13105-016-0524-2. Epub 2016 Oct 14.

Abstract

Human diploid fibroblasts (HDFs) proliferation in culture has been used as a model of aging at the cellular level. Growth arrest is one of the most important mechanisms responsible for replicative senescence. Recent researches have been focusing on the function of vitamin E in modulating cellular signaling and gene expression. Therefore, the aim of this study was to elucidate the effect of palm γ-tocotrienol (vitamin E) in modulating cellular aging through p16INK4a pathway in HDF cells. Primary culture of senescent HDFs was incubated with 70 μM of palm γ-tocotrienol for 24 hours. Silencing of p16INK4a was carried out by siRNA transfection. RNA was extracted from the different treatment groups and gene expression analysis was carried out by real-time reverse transcription polymerase chain reaction. Proteins that were regulated by p16INK4a were determined by western blot technique. The finding of this study showed that p16INK4a mRNA was overexpressed in senescent HDFs, and hypophosphorylated-pRb and cyclin D1 protein expressions were increased (p < 0.05). However, downregulation of p16INK4a and hypophosphorylated-pRb and cyclin D1 protein expressions (p < 0.05) by γ-tocotrienol led to modulation of the cell cycle regulation during cellular aging. In conclusion, senescent HDFs showed change in biological process specifically in cell cycle regulation with elevated expression of genes and proteins which may contribute to cell cycle arrest. Palm γ-tocotrienol may delay cellular senescence of HDFs by regulating cell cycle through downregulation of p16INK4a and hypophosphorylated-pRb and cyclin D1 protein expressions.

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The Effects of Tocotrienol and Lovastatin Co-Supplementation on Bone Dynamic Histomorphometry and Bone Morphogenetic Protein-2 Expression in Rats with Estrogen Deficiency.

Chin KY, Abdul-Majeed S, Mohamed N, Ima-Nirwana S.

Nutrients. 2017 Feb 15;9(2). pii: E143. doi: 10.3390/nu9020143.

Abstract

Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2) gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The baseline was sacrificed upon receipt. All other groups were ovariectomized, except for the sham group. The ovariectomized groups were administered orally daily with (1) lovastatin 11 mg/kg/day alone; (2) tocotrienol derived from annatto bean (annatto tocotrienol) 60 mg/kg/day alone; (3) lovastatin 11 mg/kg/day, and annatto tocotrienol 60 mg/kg/day. The sham and ovariectomized control groups were treated with equal volume of vehicle. After eight weeks of treatment, the rats were sacrificed. Their bones were harvested for bone dynamic histomorphometry and BMP-2 gene expression. Rats supplemented with annatto tocotrienol and lovastatin concurrently demonstrated significantly lower single-labeled surface, but increased double-labeled surface, mineralizing surface, mineral apposition rate and bone formation rate compared to individual treatments (p < 0.05). There was a parallel increase in BMP-2 gene expression in the rats receiving combined treatment (p < 0.05). The combination of annatto tocotrienol and lovastatin exerted either additively or synergistically on selected bone parameters. In conclusion, tocotrienol can augment the bone formation and mineralization in rats receiving low-dose statins. Supplementation of tocotrienol in statin users can potentially protect them from osteoporosis.

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