Abstract
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.
Highlights
Breast cancer is the most common form of cancer in women worldwide with an estimated 1.8 million new cases and approximately 471,000 deaths in 2013 [1,2]
This study aimed to determine the effect of ALA alone and combined with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at the blood molar ratios seen in either humans (1.0:1.0:2.5, ALA:EPA:DHA) or animals (1.0:0.4:3.1, ALA:EPA:DHA) post Flaxseed contains oil (FSO) consumption on MCF-7 cell viability, miR-21 and one of its targets, phosphatase and tension homolog (PTEN) expression
MCF-7 cells were treated with ALA, combined with EPA and DHA, at ratios observed post-FSO consumption
Summary
Breast cancer is the most common form of cancer in women worldwide with an estimated 1.8 million new cases and approximately 471,000 deaths in 2013 [1,2]. Many patients and clinicians are turning towards complementary medicine, including functional foods, to improve the effectiveness and tolerability of conventional treatments [3]. These include flaxseed (FS; Linum usitatissimum) and fish oil (FO), two sources of omega-3 polyunsaturated fatty acids (n-3 PUFA) [4]. In vitro studies are useful in this context since mammalian breast cancer cells lack the necessary desaturase enzyme to convert ALA to EPA and DHA [8]. No in vitro studies have looked at the miRNA-mediated response of breast cancer cells to ALA alone or ALA:EPA:DHA combination at molar blood ratios observed previously in vivo post-ALA consumption [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
