Flaxseed (FS) has a breast tumor-reducing effect, possibly because of its high content of secoisolariciresinol diglucoside (SDG) lignan. Sesame seed (SS) is rich in the lignan sesamin (SES) but is ...non-protective. Both lignans are metabolized to estrogen-like enterodiol and enterolactone. The objective of this study was to differentiate the effects of SDG and SES on established human estrogen receptor-positive breast tumors (MCF-7) in athymic mice with high serum estrogen to help explain the different effects of FS and SS. Mice were fed for 8 wk the basal diet (BD, control) or BD supplemented with 1 g/kg SDG or SES. SES reduced palpable tumor size by 23% compared to control, whereas SDG did not differ from SES or control. Both treatments reduced tumor cell proliferation, but only SES increased apoptosis. SDG and SES reduced human epidermal growth factor receptor 2 and endothelial growth factor receptor expressions, but only SES reduced downstream pMAPK. Neither treatment affected IGF-1R, vascular endothelial growth factor receptor-2, Akt, pAkt, or MAPK of the growth factor signaling pathway. Thus, at high serum estrogen levels, SDG may not account for the tumor reducing effect of FS. SES was more effective than SDG in reducing breast tumor growth, but its effect may have been lost when consumed as a component of SS.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Flaxseed (FS) has been shown to attenuate mammary tumorigenesis, possibly due to its high α-linolenic acid (ALA)-rich oil (FSO) content. This study determined the effect of FSO on the growth of ...estrogen receptor-positive human breast tumors (MCF-7) in ovariectomized athymic mice at high premenopausal-like estrogen (E2) levels. Mice with established MCF-7 tumors were fed basal diet (control) or basal diet supplemented with FSO (40 g/kg) for 8 wks. Compared with control, FSO reduced tumor size (33%, p<0.05) and tumor cell proliferation (38%, p<0.05) and increased apoptosis (110%, p<0.001). FSO also reduced human epidermal growth factor receptor-2 (79%, p<0.05) and epidermal growth factor receptor (57%, p=0.057) expression, which then may have led to a reduction in Akt (54%, p<0.05) and phosphorylation of mitogen-activated protein kinase (MAPK) to phosphorylated MAPK (pMAPK, 28%, p<0.05). Insulin-like growth factor-1 receptor, vascular endothelial growth factor receptor, MAPK and phosphorylated Akt were not affected. FSO increased (p<0.001) serum ALA, eicosapentaenoic acid and docosahexaenoic acid and, in vitro, ALA reduced MCF-7 cell proliferation (33%, p<0.001). Thus, FSO regressed estrogen receptor-positive human breast tumorigenesis at high E2 levels via downregulation of the growth factor mediated pathway, likely through its ALA content, and may explain the anti-tumorigenicity of FS.
The effects of tree nuts on risk factors for coronary heart disease (CHD), in particular blood lipids, have been investigated in a number of studies and the beneficial effects are now recognized. The ...beneficial effects of nuts on CHD in cohort studies have also been clearly demonstrated. However, while there is also reason to believe the unique micro- and macronutrient profiles of nuts may help to control blood glucose levels, relatively few studies have investigated their role in diabetes control and prevention. Nuts are low in available carbohydrate, have a healthy fatty acid profile, and are high in vegetable protein, fiber and magnesium. Acute feeding studies indicate that when eaten alone nuts have minimal effects on raising postprandial blood glucose levels. In addition, when nuts are consumed with carbohydrate rich foods, they blunt the postprandial glycemic response of the carbohydrate meal. Despite the success of these acute studies, only a limited number of trials have been conducted with nuts in type 2 diabetes. These studies have either been of insufficient duration to observe changes in HbA1c, as the standard measure of glycemic control, or have been underpowered. Therefore, more long-term clinical trials are required to examine the role of nuts on glycemic control in patients with prediabetes and diabetes. Overall, there are good reasons to justify further exploration of the use of nuts in the prevention of diabetes and its micro- and macrovascular complications.
Diets rich in fruits and vegetables (FV) have been associated with a reduced risk of chronic disease, including cardiovascular disease. Unfortunately, public health campaigns to increase FV intake ...have had limited success. A number of mixed concentrated FV products have been studied, which may help certain individuals improve nutrient status. However, the possible health benefits of FV supplements have not been systematically reviewed. We, therefore, undertook a systematic search of MEDLINE and EMBASE to identify clinical interventions that examined the effect of commercially available concentrated mixed FV supplements on cardiovascular disease risk factors. Twenty-two reports, which used commercially available products, were identified. None of the studies reported any serious adverse effects. Overall, daily consumption of FV supplements significantly increased serum concentrations of the major antioxidant provitamins and vitamins found in plant foods (β-carotene, vitamins C and E) and folate. Functional changes, such as reduced serum homocysteine and markers of protein, lipid, and DNA oxidation, were also reported; in addition, the health advantages on markers of inflammation, immunity, and endothelial function are promising. Limitations of the available studies were related to the diversity of studies conducted with respect to design and study population and the variability in the measured outcomes and assays utilized. While mixed FV supplements may serve as an efficacious complement for individuals who have difficulty achieving their daily FV intake requirement, further research on additional retail preparations is warranted.
Key teaching points:
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Mixed fruit and vegetable supplements produced from plant foods may serve as an efficacious complement to the habitual diet in individuals who have suboptimal intake or variety of nutrient-dense fruits and vegetables.
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Current research indicates that fruit and vegetable concentrates significantly increase serum levels of antioxidant provitamins and vitamins (β-carotene, vitamins C and E) and folate and reduce homocysteine and markers of oxidative stress.
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Mechanistic studies and larger, randomized, placebo-controlled double-blind trials in both healthy and high-risk populations are necessary to better understand the health effects of these supplements.
Abstract only
Flaxseed (FS) reduces breast cancer growth perhaps due to its high lignan (secoisolariciresinol diglycoside (SDG)) and α‐linolenic acid (ALA)‐rich oil (FSO) content. Sesame seed (SS), ...which is also rich in lignans like sesamin (SES) but low in ALA, is tumorigenic. Like SDG, SES is converted to estrogen‐like enterodiol (ED) and enterolactone (EL). Our objective is to determine the effects of SES, SDG and FSO on breast tumor growth to explain the opposing effects of FS and SS. Estrogen‐positive breast tumor cells (MCF‐7) were tested for proliferation
in vitro
after 4‐day treatment with ALA (50uM), SES (1uM), ED and EL (1uM). Only ALA reduced proliferation (33%, P<0.001). Ovariectomized mice with MCF‐7 tumors were fed for 8 weeks the basal diet (BD; control) or BD supplemented with 0.1% SDG, 0.1% SES, or 4.0% FSO, at levels found in 10% FS or SS diets. Compared to control, SES and FSO reduced palpable tumor area by 23% (P<0.05) and 33% (P<0.01), respectively. FSO reduced tumor volume and weight (both 37%, P<0.05), while SES caused decreases of 21% and 25%, respectively, though not different from control or FSO. SDG had no effect. SES and FSO increased apoptosis by 91% and 110% (P<0.01), respectively, and decreased proliferation by 38% (P<0.01). SDG did not affect apoptosis but reduced proliferation by 37% (P<0.05). Thus, ALA may account for the protectiveness of FS and SES may not account for the tumorigenicity of SS. (Funded by NSERC)
Increased intake of fruit and vegetable (FV) has been associated with a reduced risk of chronic diseases, including cardiovascular disease (CVD). However, public health campaigns to increase FV ...intake have had limited success. A variety of mixed FV concentrates are available in the marketplace which may help certain individuals to achieve FV intake recommendations. However, the possible CVD benefits of FV concentrates have not been systematically reviewed. Our purpose, therefore, was to review the clinical trials that have studied the effects of these concentrates on CVD risk factors. A systematic search of EMBASE and MEDLINE databases identified 12 randomized, controlled clinical trials of 2 weeks duration or longer, which reported on at least one CVD risk factor. These studies assessed markers of oxidative stress (e.g. protein carbonyls, interleukin‐6), endothelial function and homocysteine. Daily consumption of FV concentrates significantly increased serum concentrations of antioxidant vitamins in 5 of 6 studies and significantly improved at least one marker (oxidative stress, endothelial function, homocysteine) of CVD risk in 10 of 12 studies. While longer term studies are required, these data indicate that FV concentrates may be of benefit in terms of improving antioxidant vitamin status, decreasing oxidative stress and reducing certain risk factors for CVD. (The study is not funded)
Abstract only
TRAS is the primary drug for breast tumors that overexpress epidermal growth factor receptor 2 (HER2) but tumors develop resistance within 1 year of treatment. Our objective is to ...determine whether combining dietary ALA‐rich FO with TRAS treatment will enhance TRAS effectiveness. HER2 overexpressing breast tumor cells (BT‐474) were tested for proliferation and HER2 level
in vitro
after treatment with ALA (50µM), TRAS (10µg/ml) or their combination. Compared with untreated control, ALA, TRAS and combination caused a 35%, 54% and 61% reduction in proliferation and a 23% increase and 19% and 88% reduction in HER 2 expression (p<0.05), respectively. Ovariectomized mice with BT‐474 tumors were fed the basal diet (BD) (control) or treated with TRAS (2.5 or 5mg/kg) and fed either the BD or BD supplemented with 8% FO for 4 weeks. Compared to control, both TRAS and FO+TRAS treatments caused significant reductions in tumor growth over time (P<0.05). Control tumors increased in size by 63% while tumor size with FO+TRAS2.5 was reduced by 85% which is greater than that with TRAS2.5 (16%) (p<0.05) and not significantly different from that with TRAS5, alone or with FO. FO+TRAS2.5 caused greater reduction ( 85%) in cell proliferation (Ki67 labeling index) than with TRAS2.5 alone (59%; p<0.05). In conclusion, ALA and ALA‐rich FO enhanced TRAS effects and combined FO and low dose TRAS was just as effective as high dose TRAS.
Grant Funding Source
NSERC
The effects of tree nuts on risk factors for coronary heart disease (CHD), in particular blood lipids, have been investigated in a number of studies and the beneficial effects are now recognized. The ...beneficial effects of nuts on CHD in cohort studies have also been clearly demonstrated. However, while there is also reason to believe the unique micro- and macronutrient profiles of nuts may help to control blood glucose levels, relatively few studies have investigated their role in diabetes control and prevention. Nuts are low in available carbohydrate, have a healthy fatty acid profile, and are high in vegetable protein, fiber and magnesium. Acute feeding studies indicate that when eaten alone nuts have minimal effects on raising postprandial blood glucose levels. In addition, when nuts are consumed with carbohydrate rich foods, they blunt the postprandial glycemic response of the carbohydrate meal. Despite the success of these acute studies, only a limited number of trials have been conducted with nuts in type 2 diabetes. These studies have either been of insufficient duration to observe changes in HbA1c, as the standard measure of glycemic control, or have been underpowered. Therefore, more long-term clinical trials are required to examine the role of nuts on glycemic control in patients with prediabetes and diabetes. Overall, there are good reasons to justify further exploration of the use of nuts in the prevention of diabetes and its micro- and macrovascular complications.
Whole flaxseed (FS) reduces mammary tumourigenesis, possibly due to its high lignan (secoisolariciresinol diglycoside, SDG) and/or a-linolenic acid (ALA)-rich oil (FSO) content. Sesame seed (SS) is ...sesamin (SES) lignan-rich and ALA-deficient, but non-protective. Like SDG, SES metabolizes to estrogen-like enterodiol (ED) and enterolactone (EL). This study determined the effects of SES, SDG and FSO on MCF-7 tumourigenesis in athymic mice under high estrogen levels to differentiate whole FS and SS effects. Only SES and FSO reduced palpable tumour size. SES and FSO increased apoptosis, while all treatments reduced proliferation, HER2 and EGFR expressions. FSO reduced Akt expression, while SES and FSO reduced pMAPK. No treatments affected IGF-1R, VEGFR, MAPK or pAkt. Only FSO increased serum ALA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA. but not SES, ED or EL, reduced proliferation in vitro . Thus, ALA, EPA and/or DHA of FSO may explain the anti-tumourigenicity of whole FS versus SS.
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