Abstract
The implication of inflammation in pathophysiology of several type of cancers has been under intense investigation. Omega-3 fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. Pyroptosis is an inflammation related cell death and so far, the function of docosahexaenoic acid (DHA) in pyroptosis cell death has not been described. This study investigated the role of DHA in triggering pyroptosis activation in breast cancer cells. MDA-MB-231 breast cancer cells were supplemented with DHA and inflammation cell death was analyzed. DHA-treated breast cancer cells triggered increased caspase-1and gasdermin D activation, enhanced IL-1β secretion, translocated HMGB1 towards the cytoplasm, and membrane pore formation when compared to untreated cells, suggesting DHA induces pyroptosis programmed cell death in breast cancer cells. Moreover, caspase-1 inhibitor (YVAD) could protect breast cancer cells from DHA-induced pyroptotic cell death. In addition, membrane pore formation showed to be a lysosomal damage and ROS formation-depended event in breast cancer cells. DHA triggered pyroptosis cell death in MDA-MB-231by activating several pyroptosis markers in these cells. This is the first study that shows the effect of DHA triggering pyroptosis programmed cell death in breast cancer cells and it could improve the understanding of the omega-3 supplementation during breast cancer treatment.
Highlights
The implication of inflammation in pathophysiology of several type of cancers has been under intense investigation
We hypothesized whether the cellular cytotoxicity induced by omega-3 Docosahexaenoic acid (DHA) could be mediated by pyroptosis cell death in breast cancer cells
We have demonstrated here that DHA but not arachidonic acid (AA) can induce pyroptosis cell death in triple-negative MDA-MB-231 breast cancer cells
Summary
The implication of inflammation in pathophysiology of several type of cancers has been under intense investigation. It refers to breast cancers that do not express genes for estrogen receptor, progesterone receptor and epidermal growth factor receptor 2 and do not respond to therapies targeted to these receptors[1,2] This type of breast cancer is more aggressive and has higher recurrence and death rates than other subtypes in the first years after treatment[3,4]. MDA-MB-231 human cells express this triple-negative immunoprofile and are the main cell line used to investigate this breast cancer subtype[5,6]. They are flattened and spindle-like cells with increased cell-cell contacts and an aggressive phenotype[7]. This form of cell death is a programmed process mediated by proteases so-called inflammatory caspases (caspases-1, -4, -5 in humans and -11 in mice) activated within inflammasomes, that will culminate to pore formation in cell www.nature.com/scientificreports/
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