Apoptosis is induced by docosahexaenoic acid in breast cancer cells via death receptor and mitochondria-mediated pathways

Abstract

In the present study, the antitumor effect of n‑3 fatty acid was evaluated, and the effect of docosahexaenoic acid (DHA) on the induction of apoptosis and its underlying mechanism were examined. Flow cytometry and western blot analysis were performed to analyze apoptosis and the expression of protein factors in human breast cancer cells. The data revealed that DHA inhibited the viability of MCF‑7 breast cancer cells in vitro, and promoted cell death by the induction of apoptosis. DHA decreased the expression of B‑cell lymphoma 2 (Bcl‑2), whereas the expression of Bcl‑2‑associated X protein was increased. DHA was also shown to promote the release of Smac/Diablo and cytochrome c from the mitochondria. DHA increased the levels of cleaved caspase‑8, ‑9 and ‑3. Additionally, the protein expression of tumor necrosis factor‑related apoptosis‑inducing ligand, death receptor 4 and Fas were increased following DHA treatment. In conclusion, DHA caused apoptosis of the human breast cancer cells in vitro through the death receptor and mitochondria‑mediated pathways. The results of this study encourage further investigation of the effect of fish oil on the prevention and treatment of human breast cancer.

Omega 3-DHA and Delta-Tocotrienol Modulate Lipid Droplet Biogenesis and Lipophagy in Breast Cancer Cells: the Impact in Cancer Aggressiveness

“…Thus, studies focusing on the investigation of its molecular mechanisms and description of bioactive molecules that could help in adjuvant clinical treatments, influencing tumor growth, could have major importance in breast cancer therapy. It is well known that DHA is beneficial for inhibiting breast tumor carcinogenesis by triggering breast cancer cell death at 100 to 200 μM doses in vitro [35,41]. However, our present data showed that DHA at 50 μM can also induce an increased amount of LD biogenesis in MDA-MB-231 breast cancer cells and that higher LD cytoplasmic content can be correlated with higher cancer aggressiveness.…”

Curcumin- and Piperine-Loaded Emulsomes as Combinational Treatment Approach Enhance the Anticancer Activity of Curcumin on HCT116 Colorectal Cancer Model

“…Thus, this further explains the occurring morphological changes of HCT116 cells when treated with combination therapy. Induction of apoptosis in various type of cancer cells was reported for curcumin to occur via mitochondrial and receptor-mediated apoptotic pathways, where caspases play key role (Philchenkov et al, 2004;Xue et al, 2017).…”

Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

“…More specifically for breast cancer, several intracellular targets have been identified as being involved in the DHA effect, among which the PKB/akt, and p53 pathways and increased caspase activity (reviewed in [18,23]). Additional mechanisms involved in the pro-apoptotic effect of DHA in breast cancer cells include, but are not limited to, decreased Erk activity [28,29], increased Bax pro-apoptotic enzyme levels or activity and decreased Bcl-XL, increased death receptors (DR-4, TRAIL, and Fas) expression and mitochondrial release of the caspase activator SMAC/Diablo in the MCF-7 cell line [30], PPAR-α overexpression in breast cancer tissue or cells [31,32], increased expression of the stress-induced growth inhibitor 1 (OSGIN1) and transcription factor NFE2L2 in MCF-7 and Hs578T breast cancer cells [33]. However, DHA also increased the activity of antioxidant enzymes (SOD, CAT, and GPX) in breast cancer tissues [31], suggesting that the anti-/pro-oxidant effects of DHA may be dependent on the cell type and concentration used.…”