Anticancer effects of methotrexate in combination with α‑tocopherol and α‑tocopherol succinate on triple‑negative breast cancer

Wei CW, Yu YL, Chen YH, Hung YT, Yiang GT

Oncol Rep. 2019 Mar;41(3):2060-2066. doi: 10.3892/or.2019.6958. Epub 2019 Jan 9.

Abstract

Triple‑negative breast cancers (TNBCs) lack the estrogen receptor, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Therefore, hormone or targeted therapies are not effective in the treatment of TNBC and thus the development of novel therapeutic strategies is crucial. Methotrexate (MTX), a folate antagonist, has been used in the treatment of various types of cancer; however, the anticancer effects of MTX treatment on breast cancer have thus far been ineffective. Vitamin E variants and derivatives have been applied for cancer therapy. Previous studies have indicated that vitamin E variants and derivatives exert distinct anticancer effects on different types of cancer. However, whether MTX plus vitamin E variants or its derivatives can inhibit TNBC remains unclear. The aim of the present study was to examine the anticancer effects and mechanisms of action of MTX in combination with vitamin E variants (α‑tocopherol) and derivatives (α‑tocopherol succinate) on TNBC. In the present study, MTT assay and western blot analysis were used to determine the cell survival rates and protein levels. The results demonstrated that combination treatment with MTX and α‑tocopherol suppressed TNBC cell proliferation. In addition, various concentrations of MTX exerted distinct cytotoxic effects on α‑tocopherol succinate‑treated cells. Furthermore, high‑dose MTX enhanced α‑tocopherol succinate‑induced anticancer activity; however, low‑dose MTX inhibited α‑tocopherolsuccinate‑induced anticancer activity. The present study also demonstrated that caspase‑3 activation and poly(adenosine diphosphate‑ribose) polymerase cleavage were observed in the α‑tocopherol succinate/MTX‑treated cells. In conclusion, the findings of the present study demonstrated that high‑dose MTX enhanced anticancer activity in α‑TOS‑treated TNBC, while low‑dose MTX reduced anticancer activity in α‑TOS‑treated TNBC.

Read More

Delta tocotrienol in recurrent ovarian cancer. A phase II trial

Thomsen CB, Andersen RF, Steffensen KD, Adimi P, Jakobsen A

Pharmacol Res. 2019 Mar;141:392-396. doi: 10.1016/j.phrs.2019.01.017. Epub 2019 Jan 9.

Abstract

Delta tocotrienol has anti-neoplastic activity as demonstrated in several in-vitro and in-vivo investigations. The effect relies on inhibition of different pathways. It also has antiangiogenic activity, and an additive effect to bevacizumab may be expected. The present study was a phase II trial of bevacizumab combined with tocotrienol in chemotherapy refractory ovarian cancer. The study also included analysis of circulating tumor specific HOXA9 methylated DNA (HOXA9 meth-ctDNA) during treatment. The study included 23 patients. The rate of disease stabilization was 70% with very low toxicity. The median PFS was 6.9 months and the median OS 10.9 months, which is rather high compared to the current literature. A division of the patients according to level of HOXA9 meth-ctDNA already after the first cycle of chemotherapy resulted in two groups of patients with different prognoses. Patients with an increasing level of HOXA9 meth-ctDNA had a median PFS and OS of 1.4 and 4.3 months, respectively, compared to 7.8 and 12 months in the group with stable or decreasing levels. The combination of bevacizumab and tocotrienol is potent in chemotherapy refractory ovarian cancer. The level of HOXA9 meth-ctDNA after one cycle of chemotherapy holds important prognostic information.

Read More

A novel nitroalkene-α-tocopherol analogue inhibits inflammation and ameliorates atherosclerosis in Apo E knockout mice

Rodriguez-Duarte J, Galliussi G, Dapueto R, Rossello J, Malacrida L, Kamaid A, Schopfer FJ, Escande C, López GV, Batthyány C

Br J Pharmacol. 2019 Mar;176(6):757-772. doi: 10.1111/bph.14561. Epub 2019 Feb 3.

Abstract

BACKGROUND AND PURPOSE:

Atherosclerosis is characterized by chronic low-grade inflammation with concomitant lipid accumulation in the arterial wall. Anti-inflammatory and anti-atherogenic properties have been described for a novel class of endogenous nitroalkenes (nitrated-unsaturated fatty acids), formed during inflammation and digestion/absorption processes. The lipid-associated antioxidant α-tocopherol is transported systemically by LDL particles including to the atheroma lesions. To capitalize on the overlapping and complementary salutary properties of endogenous nitroalkenes and α-tocopherol, we designed and synthesized a novel nitroalkene-α-tocopherol analogue (NATOH) to address chronic inflammation and atherosclerosis, particularly at the lesion sites.

EXPERIMENTAL APPROACH:

We synthesized NATOH, determined its electrophilicity and antioxidant capacity and studied its effects over pro-inflammatory and cytoprotective pathways in macrophages in vitro. Moreover, we demonstrated its incorporation into lipoproteins and tissue both in vitro and in vivo, and determined its effect on atherosclerosis and inflammatory responses in vivo using the Apo E knockout mice model.

KEY RESULTS:

NATOH exhibited similar antioxidant capacity to α-tocopherol and, due to the presence of the nitroalkenyl group, like endogenous nitroalkenes, it exerted electrophilic reactivity. NATOH was incorporated in vivo into the VLDL/LDL lipoproteins particles to reach the atheroma lesions. Furthermore, oral administration of NATOH down-regulated NF-κB-dependent expression of pro-inflammatory markers (including IL-1β and adhesion molecules) and ameliorated atherosclerosis in Apo E knockout mice.

CONCLUSIONS AND IMPLICATIONS:

In toto, the data demonstrate a novel pharmacological strategy for the prevention of atherosclerosis based on a creative, natural and safe drug delivery system of a non-conventional anti-inflammatory compound (NATOH) with significant potential for clinical application.

Read More

Dietary vitamin E affects small intestinal histomorphology, digestive enzyme activity, and the expression of nutrient transporters by inhibiting proliferation of intestinal epithelial cells within jejunum in weaned piglets1

Chen C, Wang Z, Li J, Li Y, Huang P, Ding X, Yin J, He S, Yang H, Yin Y

J Anim Sci. 2019 Mar 1;97(3):1212-1221. doi: 10.1093/jas/skz023.

Abstract

Vitamin E (VE) is an indispensable vitamin in piglet feed formula. Among other things, it affects tissues including small intestine tissues and in particular its major unit intestinal epithelial cells. Previously, limited in vivo experiments have focused on the effect of VE on the intestine, particularly digestion and absorption. VE has been shown to inhibit proliferation of some types of cells. This experiment was conducted to test the hypothesis that VE affects intestinal functions by influencing the intestinal epithelial cell proliferation. Thirty 21-d old weaned [(Yorkshire × Landrace) × Duroc] piglets with BWs of 6.36 ± 0.55 kg were randomly divided into five VE-containing feeding formula groups. The treatments were (i) 0 IU (control), (ii) 16 IU, (iii) 32 IU, (iv) 4. 80 IU, and (v) 5. 160 IU. The treatments lasted 14 d. At the end of the experiment, all subjects were sacrificed to obtain blood and tissue samples. The results suggest that VE did not affect the growth performance. VE did tend to decrease jejunal crypt depth (linear, P = 0.056) and villus width (linear, P < 0.05). Sucrase activity significantly decreased in the adding 80 IU VE compared with the control (P < 0.05). Jejunal crypt, cell proliferation in 80 IU group significantly decreased compared with the control group (P < 0.05). This study suggests that dietary VE may affect intestinal morphology and functions by inhibiting weaned piglet jejunal epithelial cell proliferation.

Read More

Vitamin E supplementation in chronically hemodialyzed patients – influence on blood hemoglobin and plasma (anti)oxidant status

Ruskovska T, Pop-Kostova A, Hjm Jansen E, Antarorov R, Gjorgoski I

Int J Vitam Nutr Res. 2019 Feb 27:1-10. doi: 10.1024/0300-9831/a000471. [Epub ahead of print]

Abstract

BACKGROUND:

Disturbed oxidant/antioxidant status is involved in pathogenesis of anemia in end stage renal disease. There is evidence that vitamin E supplementation can increase blood hemoglobin in chronically hemodialyzed patients. However, the interindividual variation in response to the supplementation has not been fully addressed.

METHODS:

24 chronically hemodialyzed patients were supplemented with vitamin E (400 IU/day) in a period of two months. They had already been treated with erythropoiesis stimulating agents (ESA) and iron on a long-term basis, which was continued during the study period. A group of 20 healthy volunteers served as control subjects. Complete blood count, general biochemistry assays, the redox status by total thiols, oxidative stress by reactive oxygen metabolites, antioxidant status by biological antioxidant potential, and vitamin E (α- and γ- tocopherol) were measured before the start of supplementation, one month and two months later.

RESULTS:

Overall, the vitamin E supplementation did not cause an increase of blood hemoglobin, hematocrit or red blood cells. However, 50 % of the patients with basal blood hemoglobin below 12.0 g/dL (N = 10) responded to the supplementation with its continuous increase. In addition, vitamin E exhibited a slight prooxidant effect only in the subgroup of patients with basal blood hemoglobin of ≥ 12.0 g/dL, two months after the start of supplementation (decreased total thiols: 300 ± 31 vs. 277 ± 36 µmol/L, p < 0.05; increased reactive oxygen metabolites: 183 ± 140 vs. 287 ± 112 CARR U, p > 0.05; decreased biological antioxidant potential: 2278 ± 150 vs. 2171 ± 126 µEq/L, p < 0.025), which coincided with their significantly increased serum α-tocopherol concentrations in comparison to the patients with basal blood hemoglobin below 12.0 g/dL (41.3 ± 7.2 vs. 59.9 ± 19.2 µmol/L, p < 0.025).

CONCLUSIONS:

When treated with ESA and iron on a long-term basis, the response to the vitamin E supplementation in chronically hemodialyzed patients is largely dependent on their basal blood hemoglobin and serum vitamin E concentrations.

Read More

Nutritional modulation of the antioxidant capacities in poultry: the case of vitamin E

Surai PF, Kochish II, Romanov MN, Griffin DK

Poult Sci. 2019 Feb 26. pii: pez072. doi: 10.3382/ps/pez072. [Epub ahead of print]

Abstract

Commercial poultry production is associated with a range of stresses, including environmental, technological, nutritional, and internal/biological ones, responsible for decreased productive and reproductive performance of poultry. At the molecular level, most of them are associated with oxidative stress and damages to important biological molecules. Poultry feed contains a range of feed-derived and supplemented antioxidants and, among them, vitamin E is considered as the “headquarters” of the antioxidant defense network. It is well-established that dietary supplementation of selenium, vitamin E, and carotenoids can modulate antioxidant defenses in poultry. The aim of the present paper is to present evidence related to modulation of the antioxidant capacities in poultry by vitamin E. Using 3 model systems including poultry breeders/males, semen, and chicken embryo/postnatal chickens, the possibility of modulation of the antioxidant defense mechanisms has been clearly demonstrated. It was shown that increased vitamin E supplementation in the breeder’s or cockerel’s diet increased their resistance to various stresses, including high polyunsaturated fatty acids (PUFA), mycotoxin, or heat stress. Increased vitamin E supplementation of poultry males was shown to be associated with significant increases in α-tocopherol level in semen associated with an increased resistance to oxidative stress imposed by various external stressors. Similarly, increased vitamin E concentration in the egg yolk due to dietary supplementation was shown to be associated with increased α-tocopherol concentration in the tissues of the developing embryos and newly hatched chicks resulting in increased antioxidant defenses and decreased lipid peroxidation. Furthermore, increased vitamin E transfer from the feed to egg yolk and further to the developing embryo was shown to be associated with upregulation of antioxidant enzymes reflecting antioxidant system regulation and adaptation. The role of vitamin E in cell signaling and gene expression as well as in interaction with microbiota and maintaining gut health in poultry awaits further investigation.

Read More

Vitamin E consumption and the risk of bladder cancer

Lin JH, Chen SJ, Liu H, Yan Y, Zheng JH

Int J Vitam Nutr Res. 2019 Feb 26:1-8. doi: 10.1024/0300-9831/a000553. [Epub ahead of print]

Abstract

BACKGROUND:

Vitamin E has anti-cancer properties, which was demonstrated mainly due to its antioxidant effect. Several epidemiological studies have investigated the association between vitamin E consumption and the risk of bladder cancer. However, the results were inconsistent. The meta-analysis study aimed to evaluate the association of vitamin E consumption and the risk of bladder cancer.

METHODS:

We conducted a systematic literature search in the electronic databases, which included MEDLINE, EMBASE and the Cochrane Library till 1 January 2016. The pooled relative risk ratios (RRs) with 95% confidence intervals (CIs) were calculated depending on the heterogeneity among studies. Subgroup analysis and sensitivity analysis were also performed. Publication bias was assessed using Begg’s test and Egger’s test.

RESULTS:

A total of 11 prospective studies (3 randomized clinical trials and 8 cohort studies) including 575601 participants were identified to be eligible for our present meta-analysis. The pooled RRs with 95% CI for highest versus lowest vitamin E consumption was 0.89 (0.78-1.00). An inverse linear association between vitamin E consumption and bladder cancer risk was detected in the dose response analysis. The results were also stable in the subgroup analysis and sensitivity analysis. Meanwhile, no obvious publication bias was observed.

CONCLUSIONS:

Our study indicates that vitamin E consumption was inversely associated with the risk of bladder cancer.

Read More

The neuroprotective effect of vitamin E on waterpipe tobacco smoking-induced memory impairment: The antioxidative role

Alzoubi KH, Halboup AM, Alomari MM, Khabour OF

Life Sci. 2019 Feb 25. pii: S0024-3205(19)30140-7. doi: 10.1016/j.lfs.2019.02.050. [Epub ahead of print]

Abstract

AIMS:

Tobacco smoking is associated with a vast range of adverse health effects, including diminished cognitive and anti-oxidative capabilities. Conversely, vitamin E (VitE) is known to enhance data acquisition and retention and hippocampal oxidative defense. No studies, however, examined the protective effect of VitE with tobacco administration. Therefore, this study examined the protective effect of VitE on the cognitive and oxidative debilitating effects induced by waterpipe smoking.

MATERIALS AND METHODS:

Wistar male rats were divided into four groups: waterpipe smoking, VitE, waterpipe combined with VitE, and control group. The exposure to waterpipe and VitE was for one month and then spatial learning and memory were assesses using Radial Arms Water Maze. Additionally, oxidative stress biomarkers (Catalase, GPx, and TBARS, GSH, GSSG, and GSH/GSSG ratio) were assessed in the hippocampus.

KEY FINDINGS:

The results revealed that waterpipe smoking impaired short-term and long-term memory (P < 0.05). Waterpipe smoking reduced activity of catalase (P < 0.05), GPx (P < 0.05) and GSH/GSSG ratio (P < 0.05) in the hippocampus. Administration of VitE prevented memory impairment and alterations in oxidative stress biomarkers.

SIGNIFICANCE:

waterpipe smoking induces short-term and long-term memory impairments, which were prevented by administration of VitE via its anti-oxidative properties.

Read More

The Effect of Lipid Antioxidant α-Tocopherol on Cell Viability and Electrofusion Yield of B16-F1 Cells In Vitro

Kanduser M, Kokalj Imsirovic M, Usaj M

J Membr Biol. 2019 Feb;252(1):105-114. doi: 10.1007/s00232-019-00059-4. Epub 2019 Jan 22.

Abstract

Induced cell fusion is a powerful method for production of hybridoma in biotechnology and cell vaccines in medical applications. Among different alternatives, physical methods have an advantage, as they do not require any additives. Among them electrofusion, an electroporation-based cell fusion method holds a great promise. Electric pulses cause cell membrane permeabilization and due to pore formation bring cell membrane into the fusogenic state. At the same time, however, they compromise cell viability. We used a train of 8 × 100 µs electric pulses, delivered at 1 Hz with strengths ranging from 400 to 1600 V/cm. We evaluated electrofusion efficiency by dual color microscopy. We determined cell viability, because during electroporation reactive oxygen species are generated affecting cell survival. The novelty of our study is evaluation of the effect of lipid antioxidant α-tocopherol on cell fusion yield and cell viability on mouse B16-F1 cells. Pretreatment with α-tocopherol slowed down dynamic of cell fusion shortly after electroporation. Twenty-four hours later, fusion yields between α-tocopherol treated and untreated cells were comparable. The viability of α-tocopherol pretreated cells was drastically improved. Pretreatment of cells with α-tocopherol improved whole electrofusion process by more than 60%. We believe that α-tocopherol holds great promise to become an important agent to improve cell electrofusion method.

Read More

DHA and vitamin E antagonized the Aβ25-35-mediated neuron oxidative damage through activation of Nrf2 signaling pathways and regulation of CD36, SRB1 and FABP5 expression in PC12 cells

Huang X , Zhen J , Dong S , Zhang H , Van Halm-Lutterodt N , Yuan L

Food Funct. 2019 Feb 20;10(2):1049-1061. doi: 10.1039/c8fo01713a.

Abstract

The present study was designed to explore the neuroprotective effects of docosahexaenoic acid (DHA) and/or vitamin E (VE) in vitro. The PC12 cells were pretreated with DHA and/or VE for 4 h, followed by 50 μmol L-1 Aβ25-35 treatments for another 48 h. The cells were then collected and used for the measurements of oxidative stress parameters. Real time-PCR and western blot were applied to measure fatty acid transporters, Nrf2 and its downstream antioxidant targets’ gene and protein expression. Our results indicated that the Aβ25-35 treatment inhibited cellular growth, increased intracellular ROS generation and decreased the mitochondrial membrane potential. The Aβ25-35 treatment decreased the total antioxidant capacity (T-AOC), whereas it increased the MDA levels in neuron cells. Pretreatment of cells with VE or DHA could antagonize the Aβ25-35-mediated cell growth inhibition and mitochondrial membrane potential decline. Activation of the Nrf2 signaling pathway and regulation of CD36, SRB1 and FABP5 expression were observed in DHA- and DHA + VE-pretreated cells. Our results indicated a synergistic effect of DHA and VE in antagonizing the oxidative damage caused by Aβ25-35 in the PC12 cells. The results of the present study will shed light on the application of nutritional intervention for DHA and VE in preventing neuronal damage-related diseases.

Read More

Page 1 of 10712345...102030...Last »