Down-regulation of lipid raft-associated onco-proteins via cholesterol-dependent lipid raft internalization in docosahexaenoic acid-induced apoptosis

The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease

“…EPA and DHA are readily incorporated into cells and tissues to modify membrane properties in lipid rafts as well as nonraft domains (Williams et al, 2012), including the cholesterol content, eicosanoid profiles, signal transduction processes, and gene expression . To what extent the P450-and sEH-derived metabolites of EPA and DHA actually underlie the actions of the fish oils remains to be determined, but it is interesting to note that the DHA-induced redistribution of cholesterol out of lipid rafts Stillwell, 2008, 2009;Lee et al, 2014) decreases g-secretase activity in Fig. 5.…”

“…It will be interesting to determine whether there are also differential effects of the DHAderived epoxides and diols on the association of other signaling molecules with lipid rafts (e.g., EGFR, Hsp90, Akt, and Src) or the fusion of rafts with lysosomes (Lee et al, 2014).…”

Fatty acids as modulators of neutrophil recruitment, function and survival

“…DHA has the capacity to modify lipid raft composition and then modifies cell function. In human breast cancer cell lines,Lee et al (2014) demonstrated that DHA induces lipid raft internalization, reducing their levels on cellular membranes. This effect was associated with the poor affinity of DHA to cholesterol.…”

Efeitos do ácido docosahexaenoico (DHA) e do ácido araquidônico (AA) sobre a morte celular da linhagem celular de câncer de mama MDA-MB-231

“…Foi verificado que o DHA a partir 50µM induz aumento de morte tanto por apoptose quanto por necrose. Estudos anteriores também mostraram que o DHA aumenta a morte por apoptose devido à maior ativação das caspases 3, 8 e 9, ao aumento da condensação nuclear, à clivagem de poli(ADP-ribose)polimerase e à externalização de fosfatidilserina em MDA-MB-231 (3)(4)(5)28).…”

“…O ácido docosahexaenóico (DHA -22:6 ω-3), membro da família dos ácidos graxos poli-insaturados ômega 3, tem mostrado uma ação antitumoral tanto in vivo quanto in vitro, diminuindo a proliferação e aumentando a morte por apoptose em células de câncer de mama (1)(2)(3)(4)(5). Já o ácido araquidônico (AA -20:4 ω-6), da família ômega-6, está associado ao crescimento e à progressão tumoral (6,7).…”