n–3 Polyunsaturated Fatty Acid Amides: New Avenues in the Prevention and Treatment of Breast Cancer

Abstract

Over the last decades a renewed interest in n−3 very long polyunsaturated fatty acids (PUFAs), derived mainly from fish oils in the human diet, has been observed because of their potential effects against cancer diseases, including breast carcinoma. These n−3 PUFAs mainly consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that, alone or in combination with anticancer agents, induce cell cycle arrest, autophagy, apoptosis, and tumor growth inhibition. A large number of molecular targets of n−3 PUFAs have been identified and multiple mechanisms appear to underlie their antineoplastic activities. Evidence exists that EPA and DHA also elicit anticancer effects by the conversion to their corresponding ethanolamide derivatives in cancer cells, by binding and activation of different receptors and distinct signaling pathways. Other conjugates with serotonin or dopamine have been found to exert anti-inflammatory activities in breast tumor microenvironment, indicating the importance of these compounds as modulators of tumor epithelial/stroma interplay. The objective of this review is to provide a general overview and an update of the current n−3 PUFA derivative research and to highlight intriguing aspects of the potential therapeutic benefits of these low-toxicity compounds in breast cancer treatment and care.

A Molecular Networking Strategy: High-Throughput Screening and Chemical Analysis of Brazilian Cerrado Plant Extracts against Cancer Cells

“…Recent research suggests that a diet enriched with linoleic acid is related to a reduction in the incidence of cancer [ 32 , 33 ]. Linolenic and linoleic acids may act via different mechanisms to inhibit the development of some types of cancer, especially breast cancer [ 33 , 34 , 35 ]. The G1 sub-network contains: pristimerin [M + H] + m/z 465.3012; tingenone [M + H] + m/z 421.2745; 20-oxo-20,21-seco-tingen-21-oic acid [M + H] + m/z 453.263, and other unidentified derivatives in the database.…”

“…Recent research suggests that a diet enriched with linoleic acid is related to a reduction in the incidence of cancer [32,33]. Linolenic and linoleic acids may act via different mechanisms to inhibit the development of some types of cancer, especially breast cancer [33][34][35] [36,37].…”

Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase and ethanolamides metabolism with Alzheimer’s disease

“…Notably, sleep disturbances themselves have been reported to be a risk factor for AD [60], and the identified reductions in CSF OEA would be consistent with such a physiological manifestation [61]. A recent study also suggested that the EPA-derived ethanolamide (EPEA) is a potential PPAR γ agonist [62], a transcription factor known for its neuroprotective and anti-inflammatory action [63]. Interestingly, non-fasting levels of EPEA showed positive association with MoCA in AD patients.…”

Nutraceuticals in the Mediterranean Diet: Potential Avenues for Breast Cancer Treatment

“…However, omega-3 PUFAs may also act in combination with anticancer agents to induce cell cycle arrest improving the efficacy of some drugs, such as doxorubicin [ 109 ]. In addition, the biological effects of DHA and EPA can also be exerted by their derivative molecules including DHA-dopamine (DHADA) and EPA–dopamine (EPADA) conjugates as well as DHA-ethanolamine (DHEA) and EPA-ethanolamine (EPEA) [ 111 ]. In particular, DHADA and EPADA arrested cell cycle and reduced concomitantly S-phase in MCF-7, SK-BR-3 and MDA-MB-231 cells, indicating that these molecules induced cell cycle arrest in breast cancer cells, independently of ER/PR/HER2 status [ 70 ].…”