Abstract
It has been demonstrated that ω-3 polyunsaturated fatty acids (ω-3 PUFA) may exert a beneficial role as adjuvants in the prevention and treatment of many disorders, including cardiovascular diseases and cancer. Particularly, several in vitro and in vivo preclinical studies have shown the antitumor activity of ω-3 PUFA in different kinds of cancers, and several human studies have shown that ω-3 PUFA are able to decrease the risk of a series of cardiovascular diseases. Several mechanisms have been proposed to explain their pleiotropic beneficial effects. ω-3 PUFA have also been shown to prevent harmful side-effects (including cardiotoxicity and heart failure) induced by conventional and innovative anti-cancer drugs in both animals and patients. The available literature regarding the possible protective effects of ω-3 PUFA against anthracycline-induced cardiotoxicity, as well as the mechanisms involved, will be critically discussed herein. The study will analyze the critical role of different levels of ω-3 PUFA intake in determining the results of the combinatory studies with anthracyclines. Suggestions for future research will also be considered.
Highlights
Introduction ω-3 polyunsaturated fatty acids (PUFA) are dietary factors acknowledged for their ability to induce multiple beneficial effects [1,2,3,4]
Excellent reviews [15,90] have been published on this topic, and we will hereinafter provide only a brief outline of the mechanisms so far identified. ω-3 PUFA appear as ideal candidates in preventing the development of cardiac events induced by ATC chemotherapy, since these fatty acids are known to induce benefits at a cardiovascular level by positively modulating some of the cellular processes and molecular pathways that, are harmfully altered by ATC and other chemotherapeutic agents
From the experiments performed in rats, it is possible to conclude that the level of ω-3 PUFA intake represents one of the main factors determining whether they exert protection against ATC-induced cardiotoxicity
Summary
The combined treatment of ω-3 PUFA with other already used anticancer chemotherapeutics represents the more possible application of these nutrients in cancer therapy [13]. The potential adjuvant role of ω-3 PUFA has been investigated in combination with a series of conventional drugs in a wide range of cancers (for a comprehensive review, see [13]) The ability of these fatty acids to reduce the toxic side-effects of these drugs has been largely proven [63,64,65], and several results have concurred to demonstrate their chemosensitizing effects, as well as their ability to prevent drug-resistance [66,67,68]. One important characteristic of EPI is that, even showing a very similar antitumor activity compared to DOX, it is more glucuronitated and, better excreted through bile and urine, allowing a safe use at higher doses with respect to DOX [88] The use of these drugs may often induce acquired resistance [89] and a series of harmful side effects, including mucositis, nausea, vomiting, stomatitis and, mainly, high cardiotoxicity. Excellent reviews [15,90] have been published on this topic, and we will hereinafter provide only a brief outline of the mechanisms so far identified ( paragraph). ω-3 PUFA appear as ideal candidates in preventing the development of cardiac events induced by ATC chemotherapy, since these fatty acids are known to induce benefits at a cardiovascular level by positively modulating some of the cellular processes and molecular pathways that, are harmfully altered by ATC and other chemotherapeutic agents
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