Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

Abstract

Background. Experimental, epidemiological and clinical data substantiate the beneficial role of n-3 polyunsaturated fatty acids (PUFAs) in preventing inflammation and cancer of the colon. This review covers the unsaturated docosahexaenoic fatty acid (DHA), describes some of its important cellular and molecular mechanisms, its interaction with another dietary lipid, butyrate and with endogenous apoptotic regulators of the tumour necrosis factor (TNF) family. We also discuss the clinical impact of this knowledge and the use of these lipids in colon cancer prevention and treatment. Results. From the literature, DHA has been shown to suppress the growth, induce apoptosis in colon cancer cells in vitro and decrease the incidence and growth of experimental tumours in vivo. Based on these data and our own experimental results, we describe and discuss the possible mechanisms of DHA anticancer effects at various levels of cell organization. We show that DHA can sensitize colon cancer cells to other chemotherapeutic/chemopreventive agents and affect the action of physiological apoptotic regulators of the TNF family. Conclusion. Use of n-3 PUFAs could be a relatively non-toxic form of supportive therapy for improving colon cancer treatment and slowing down or preventing its recurrence. However, it is necessary to use them with caution, based on solid scientific evidence of their mechanisms of action from the molecular to the cellular and organism levels.

Docosahexanoic acid antagonizes TNF-α-induced necroptosis by attenuating oxidative stress, ceramide production, lysosomal dysfunction, and autophagic features

“…This would be consistent with reports indicating that ceramide-induced ROS contributes to TNF-α-induced LMP in both apoptotic and non-apoptotic cell death [44], and that DHA reduces TNF-α and interleukin 1 beta (IL-1β) inflammatory signaling by downregulating the sphingomyelinase pathway [53]. It is also possible that DHA stabilizes lysosomal membranes in L929 cells exposed to TNF-α, or that DHA-mediated changes in plasma membrane properties and microdomains [54] abrogate TNF-α death signaling common to both apoptosis and necrosis.…”

Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells

“…The ω-3 PUFAs play vital roles in the normal growth and development of various cells and tissues [20,21]. DHA is one of the longest and most unsaturated fatty acids found in biological systems, with 22 carbons and six double bonds.…”

Dietary Fiber Intake Modifies the Positive Association between n–3 PUFA Intake and Colorectal Cancer Risk in a Caucasian Population

“…Experimental evidence suggests that PUFA and DF may operate together in the colon (13). Interaction of these dietary compounds in the colonic lumen can have substantial impact on the metabolism and kinetics of the colon epithelial cell population and may influence inflammation and neoplastic changes (13,56). In addition, DF may influence FA-binding proteins (FABPs), which mediate the effect of dietary FAs between and within cells (57).…”