Contribution of n-3 Long-Chain Polyunsaturated Fatty Acids to the Prevention of Breast Cancer Risk Factors

Abstract

Nowadays, diet and breast cancer are studied at different levels, particularly in tumor prevention and progression. Thus, the molecular mechanisms leading to better knowledge are deciphered with a higher precision. Among the molecules implicated in a preventive and anti-progressive way, n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs) are good candidates. These molecules, like docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, are generally found in marine material, such as fat fishes or microalgae. EPA and DHA act as anti-proliferative, anti-invasive, and anti-angiogenic molecules in breast cancer cell lines, as well as in in vivo studies. A better characterization of the cellular and molecular pathways involving the action of these fatty acids is essential to have a realistic image of the therapeutic avenues envisaged behind their use. This need is reinforced by the increase in the number of clinical trials involving more and more n-3 LC-PUFAs, and this, in various pathologies ranging from obesity to a multitude of cancers. The objective of this review is, therefore, to highlight the new elements showing the preventive and beneficial effects of n-3 LC-PUFAs against the development and progression of breast cancer.

Docosahexaenoic Acid, a Key Compound for Enhancing Sensitization to Drug in Doxorubicin-Resistant MCF-7 Cell Line

“…N-3 long-chain polyunsaturated fatty acids (PUFAs), such as DHA, are recognized as potential agents to counteract invasive breast cancer and prevent cancer in animal models [ 50 ]. In rat models with a DHA-rich diet, DHA has been shown to act synergistically with doxorubicin and enhance its effectiveness against drug-resistant cancer cells.…”

“…Enriching cell membranes with DHA has been found to promote changes in membrane properties and membrane-mediated signaling pathways that elicit anticancer responses [ 48 , 49 ]. The n-3 LCPUFA content of membrane phospholipids is a crucial component of the dynamic and asymmetric cellular membrane that can enhance the cells’ ability to respond to chemotherapy [ 50 ]. Incorporating EPA and DHA into lipid rafts increases the clustering of large raft domains, which can act as mobile docking platforms to improve cell signaling transduction through protein/lipid trafficking, leading to increased cancer cell death [ 37 , 39 , 42 , 49 , 51 , 52 , 53 , 54 , 55 , 56 ].…”

Polysaccharide dextran-based conjugate for selective co-delivery of two synergistic drugs docetaxel and docosahexaenoic acid to tumor cells

“…DHA plays many physiologic roles including regulation of membrane fluidity, neurotransmitter release, gene expression, myelination, and cell differentiation and growth (Weiser et al., 2016 ). Importantly, it is well known that DHA alone or in combination with chemotherapeutic agents induce cell cycle arrest, apoptosis, autophagy, and tumor growth inhibition by multiple mechanisms such as influencing cell membrane lipid composition, especially that of lipid raft, which leads to a significant modification of their physical–chemical properties altering the content and function of transmembrane proteins including receptors, growth factors, and ATP-binding cassette transporters (Siddiqui et al., 2011 ; Corsetto et al., 2017 ; Giordano et al., 2020 ; Chen et al., 2021 ; Y. Liu et al., 2021 ; Fodil et al., 2022 ; L. Huang et al., 2022 ). Many clinical trials revealed that supplementation with DHA/Eicosapentaenoic acid during cancer treatment could improve a variety of outcomes important to the patient and the disease process, including immune system modulation, improved weight maintenance, and increased disease-free or progression-free survival (Newell et al., 2021 ).…”

Nutraceutical-Based Nanoformulations for Breast and Ovarian Cancer Treatment

“…Important properties of omega-3 PUFAs may explain the reasons underlying their frequent inclusion in nanoformulations designed for cancer therapy, and BCa in particular. Among them, there are their powerful and widely demonstrated anti-inflammatory and anti-cancer activities [ 2 , 29 , 30 , 31 ]. Their anti-inflammatory property has been often invoked to explain their cancer-preventive effects, as well as their efficacy in inhibiting the deleterious side effects frequently associated with chemotherapy [ 32 , 33 ].…”

“…Their anti-inflammatory property has been often invoked to explain their cancer-preventive effects, as well as their efficacy in inhibiting the deleterious side effects frequently associated with chemotherapy [ 32 , 33 ]. However, plenty of preclinical studies have shown that these FAs may exert other and more direct and specific anticancer activities at molecular levels [ 30 , 34 , 35 , 36 , 37 ]. Moreover, it was also shown that they can potentially increase cancer cell sensitivity to conventional antineoplastic therapy [ 38 ].…”