The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer

Abstract

Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. Apoptosis is a programmed cell death process that efficiently eliminates damaged cells. Several studies have indicated the involvement of polyunsaturated fatty acids (PUFAs) in apoptosis, including omega-3 PUFAs such as alpha-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid. However, the role of omega-6 PUFAs, such as linoleic acid, gamma-linolenic acid, and arachidonic acid, in apoptosis is controversial, with some studies supporting their activation of apoptosis and others suggesting inhibition. These PUFAs are essential fatty acids, and Western populations today have a high consumption rate of omega-6 to omega-3 PUFAs. This review focuses on presenting the diverse molecular mechanisms evidence in both in vitro and in vivo models, to help clarify the controversial involvement of omega-3 and omega-6 PUFAs in apoptosis mechanisms in cancer.

Poly-Unsaturated Fatty Acids (PUFAs) from Cunninghamella elegans Grown on Glycerol Induce Cell Death and Increase Intracellular Reactive Oxygen Species

“…In this study, lipids from C. elegans were administered for the first time to human cancer models, and their anti-proliferative, anti-migratory, and stress-and cell deathinducing effects were observed. C. elegans was grown on industrial-grade glycerol, a byproduct of the food and soap industries, and in nitrogen-deprivation conditions, it accumulated polyunsaturated lipids rich in GLA, a molecule with well-established anticancer activity [11,54]. Previous publications have reported GLA's capability to suppress cell proliferation and induce apoptosis [55]; however, only one study has used microbial lipids (ML)s containing it, and observations have only been made on the leukemia cell line HL-60 [24].…”

“…PUFAs are categorized into the ω-3 and the ω-6 families, with members from both families having been credited with potential cytotoxic activity against cancer cells. GLA is one of the strongest candidates of these FAs concerning the mentioned activity [10][11][12]. Proposed mechanisms of action vary; however, most findings suggest changes in the membranes' ability to facilitate their transporting roles [13] and the elevation of oxidative stress levels that can stimulate the intrinsic apoptosis pathways and finally lead to cell death [14,15].…”

The value of plasma omega-3 polyunsaturated fatty acids in predicting the response and prognosis of cervical squamous cell carcinoma to concurrent chemoradiotherapy

“…The preliminary explanation can only be given by considering previous studies. The anticancer effects of EPA are mainly attributed to its ability to modulate cell death pathways, inhibit cell proliferation and induce the expression of anti-in ammatory mediators [7,29]. The mechanism by which EPA promotes apoptosis alone involves the alteration of multiple complex cellular pathways; for example, EPA was able to induce cell cycle arrest in breast cancer cell lines [30].…”

“…Many studies have shown that PUFAs act a vital role in the occurrence of malignant tumors, including the regulation of apoptosis [7,8]. Omega-3 PUFAs are one of the polysaturated fatty acids, that are mainly derived from deep-sea sh, such as sardines and herring, so they are also known as marine PUFAs [7].…”

“…Many studies have shown that PUFAs act a vital role in the occurrence of malignant tumors, including the regulation of apoptosis [7,8]. Omega-3 PUFAs are one of the polysaturated fatty acids, that are mainly derived from deep-sea sh, such as sardines and herring, so they are also known as marine PUFAs [7]. It has been widely reported in epidemiological studies because of its remarkable anti-in ammatory effects, direct inhibition of cancer expansion and tumorigenesis [9,10].…”