Exploration of mechanisms of α-linolenic acid in reducing the growth of oestrogen receptor positive breast cancer cells (MCF-7)

Mason-Ennis, Julie K.; LeMay-Nedjelski, Lauren; Wiggins, Ashleigh K.A.; Thompson, Lilian U.

doi:10.1016/j.jff.2016.04.037

Cited by 8 publications

(10 citation statements)

References 32 publications

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“…The mechanism whereby n-3 PUFAs trigger a reduction in cell viability remains unknown; however, previous work with n-3 PUFAs and cancer cells have shown n-3 PUFAs not only to reduce cell viability, as was seen in this study, but also induce apoptosis selectively in cancer cells, while leaving normal cells unharmed [ 9 , 22 , 32 ]. ALA has been found to inhibit the growth of MCF-7 cells in vitro without cytotoxicity [ 33 ].…”

Section: Discussionmentioning

confidence: 58%

“…Previous work conducted in our lab has shown that ALA is significantly incorporated into cellular phospholipids following in vitro ALA treatment, but formation of ALA metabolites, including EPA and DHA was not observed [ 8 , 9 , 22 ]. Accordingly, EPA and especially DHA have been found to be reduced in ALA-treated cells, as well as total omega-6 (n-6) PUFA and monounsaturated fatty acids being significantly lower [ 8 , 9 , 22 ]. Additionally, it has been shown that treatment with DHA increases phospholipid DHA in breast cancer cells [ 23 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Additional work by our group on the effect of ALA on apoptosis induction measured using annexin V staining in MCF-7 cells showed no significant effect [ 8 , 9 ]. Due to these findings, it was hypothesized in [ 22 ] that for ALA the growth retardation is likely due to inhibition of proliferation and not induction of apoptosis. In contrast, n-3 PUFAs EPA and DHA have been shown to induce apoptosis via alteration of B-cell lymphoma 2 (Bcl-2) and procaspase-8 and reduce cell growth in both estrogen receptor-negative and positive breast cancer cells in vitro [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

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Omega-3 Polyunsaturated Fatty Acids Time-Dependently Reduce Cell Viability and Oncogenic MicroRNA-21 Expression in Estrogen Receptor-Positive Breast Cancer Cells (MCF-7)

LeMay-Nedjelski

Mason-Ennis

Taïbi

et al. 2018

IJMS

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The omega-3 polyunsaturated fatty acid (n-3 PUFA), α-linolenic acid (ALA), and its metabolites, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), independently reduce the growth of breast cancer cells in vitro, but the mechanisms, which may involve microRNA (miRNA), are still unclear. The expression of the oncomiR, miR-21, is reduced by DHA treatment, but the effects of ALA on miR-21, alone or combined with EPA and DHA under physiologically relevant concentrations, have not been investigated. The effects of ALA alone and +/−EPA and DHA at the blood molar ratios seen in either humans (1.0:1.0:2.5, ALA:EPA:DHA) or mice (1.0:0.4:3.1, ALA:EPA:DHA) post flaxseed oil consumption (containing ALA) were assessed in vitro in MCF-7 breast cancer cells. Cell viability and the expression of miR-21 and its molecular target, phosphatase and tension homolog (PTEN, gene and protein), at different time points, were examined. At 1, 3, 48 and 96 h ALA alone and 24 h animal ratio treatments significantly reduced MCF-7 cell viability, while 1 and 3 h ALA alone and human and animal ratio treatments all significantly reduced miR-21 expression, and 24 h animal ratio treatment reduced miR-21 expression; these effects were not associated with changes in PTEN gene or protein expressions. We showed for the first time that ALA alone or combined with EPA and DHA at levels seen in human and animal blood post-ALA consumption can significantly reduce cell viability and modulate miR-21 expression in a time- and concentration-dependent manner, with the animal ratio containing higher DHA having a greater effect. The time dependency of miR-21 effects suggests the significance of considering time as a variable in miRNA studies, particularly of miR-21.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Omega-3 Polyunsaturated Fatty Acids Time-Dependently Reduce Cell Viability and Oncogenic MicroRNA-21 Expression in Estrogen Receptor-Positive Breast Cancer Cells (MCF-7)

LeMay-Nedjelski

Mason-Ennis

Taïbi

et al. 2018

IJMS

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“…In addition, linolenic acid, the fatty acid residue of DLA is an ω-3 polyunsaturated fatty acid and the precursor of eicosapentaenoic acid and docosahexaenoic acid. Diets rich in linolenic acid have been shown to inhibit tumor growth in both ER-positive and -negative breast cancer xenografts [16,19]. DLA has been previously reported in the plant Euphorbia esula [15].…”

Section: Discussionmentioning

confidence: 90%

Daucosterol linolenate from Sweet Potato Suppresses MCF7-Xenograft-Tumor Growth through Regulating PI3K/AKT Pathway

Han

Jiang

et al. 2020

Planta Med

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Sweet potato is a functional food with potential antitumor properties, but the bioactive constituents and biological mechanisms remain unclear. In this study, we investigated the antitumor effect of daucosterol linolenate extracted from sweet potato and its potential mechanism. An MTT assay indicated that DLA inhibited the proliferation of breast cancer MCF-7 cells but had only weak effects on the proliferation of MDA-MB-231, 4T1, and MCF-10A cells. Flow cytometry analysis revealed that daucosterol linolenate induced apoptosis of MCF-7 cells. Experiments with MCF-7 xenograft in nude mice further confirmed that DLA inhibited tumor growth dose-dependently. After DLA treatment, the expressions of B-cell lymphoma 2 and vascular endothelial growth factor were decreased and that of cleaved caspase 3 was increased as compared to the TC group. DLA also down-regulated the expression of phosphoinositide 3-kinase/protein kinase B and repressed insulin-induced phosphoinositide 3-kinase/protein kinase B activation. Our findings suggest that DLA suppresses breast tumor growth through inactivating the phosphoinositide 3-kinase/protein kinase B pathway.

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“…The result indicated the odd ratio for breast cancer among women in the highest quartile of adipose breast tissue ALA level compared with the lowest quartile was 0.36, proving a protective effect of ALA on breast cancer risk. Recent studies have showed that ALA reduces growth of breast cancer cell lines (MCF-7, BT-474, MDA-MB-231 and MDA-MB-468) and demonstrates a dynamic gene expression in treated breast cancer cells (Wiggins et al, 2015;Mason-Ennis et al, 2016). Hirko et al (2018) reported that there were inverse associations of n-3 PUFA (e.g.…”

Section: Ala and Cancermentioning

confidence: 99%

A brief review of physiological roles, plant resources, synthesis, purification and oxidative stability of Alpha-linolenic Acid

Tang¹,

Meng

2018

Emir J Food Agric

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Alpha-linolenic acid (ALA) is a polyunsaturated fatty acid (PUFA) comprising of 18 carbon atoms and three double bonds. Because the first double bond counted from the methyl terminus, is at position three, ALA belongs to the so-called n-3 group. Derived mainly from natural plants such as Linum usitatissimum and Perilla frutescens, it is an essential fatty acid for the human body. ALA is essential for the regulation of blood lipid, blood pressure and blood sugar, for the prevention of diseases and for the protection of retina and brain. It is the precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are crucial for human health. This review summarizes the current knowledge on physiological roles, plant resources, and synthesis, purification and oxidative stability of ALA, providing the scientific basis for its sustainable development and utilization towards human health.

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Exploration of mechanisms of α-linolenic acid in reducing the growth of oestrogen receptor positive breast cancer cells (MCF-7)

Cited by 8 publications

References 32 publications

Omega-3 Polyunsaturated Fatty Acids Time-Dependently Reduce Cell Viability and Oncogenic MicroRNA-21 Expression in Estrogen Receptor-Positive Breast Cancer Cells (MCF-7)

Omega-3 Polyunsaturated Fatty Acids Time-Dependently Reduce Cell Viability and Oncogenic MicroRNA-21 Expression in Estrogen Receptor-Positive Breast Cancer Cells (MCF-7)

Daucosterol linolenate from Sweet Potato Suppresses MCF7-Xenograft-Tumor Growth through Regulating PI3K/AKT Pathway

A brief review of physiological roles, plant resources, synthesis, purification and oxidative stability of Alpha-linolenic Acid

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