Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
Prostaglandins Leukot Essent Fatty Acids. 2020 May;156:102024. doi: 10.1016/j.plefa.2019.102024. Epub 2019 Oct 16.
The anticancer effects of the omega-3 long chain polyunsaturated fatty acids (LCPUFA), EPA and DHA may be due, at least in part, to conversion to their respective endocannabinoid derivatives, eicosapentaenoyl-ethanolamine (EPEA) and docosahexaenoyl-ethanolamine (DHEA). Here, the effects of EPEA and DHEA and their parent compounds, EPA and DHA, on breast cancer (BC) cell function was examined. EPEA and DHEA exhibited greater anti-cancer effects than EPA and DHA in two BC cells (MCF-7 and MDA-MB-231) whilst displaying no effect in non-malignant breast cells (MCF-10a). Both BC lines expressed CB receptors that were responsible, at least partly, for the observed anti-proliferative effects of the omega-3 endocannabinoids as determined by receptor antagonism studies. Additionally, major signalling mechanisms elicited by these CB ligands included altered phosphorylation of p38-MAPK, JNK, and ERK proteins. Both LCPUFAs and their endocannabinoids attenuated the expression of signal proteins in BC cells, albeit to different extents depending on cell type and lipid effectors. These signal proteins are implicated in apoptosis and attenuation of BC cell migration and invasiveness. Furthermore, only DHA reduced in vitro MDA-MB-231 migration whereas both LCPUFAs and their endocannabinoids significantly inhibited invasiveness. This finding was consistent with reduced integrin β3 expression observed with all treatments and reduced MMP-1 and VEGF with DHA treatment. Attenuation of cell viability, migration and invasion of malignant cells indicates a potential adjunct nutritional therapeutic use of these LCPUFAs and/or their endocannabinoids in treatment of breast cancer.
ω-3 长链多不饱和脂肪酸 (LCPUFA)、EPA 和 DHA 的抗癌作用可能部分归因于它们分别转化为各自的内源性大麻素衍生物，二十碳五烯酰乙醇胺 (EPEA) 和二十二碳六烯酰乙醇胺 (DHEA)。在这里，研究了 EPEA 和 DHEA 及其母体化合物 EPA 和 DHA 对乳腺癌 (BC) 细胞功能的影响。EPEA 和 DHEA 在两种 BC 细胞 (MCF-7 和 MDA-MB-231) 中表现出比 EPA 和 DHA 更强的抗癌作用，而在非恶性乳腺细胞 (MCF-10a) 中则没有作用。这两条 BC 线都表达了 CB 受体，这些受体至少部分负责观察到的 ω-3 内源性大麻素的抗增殖作用，这是通过受体拮抗研究确定的。此外，这些 CB 配体引起的主要信号机制包括 p38-MAPK、JNK 和 ERK 蛋白的磷酸化改变。两种 LCPUFA 及其内源性大麻素都能减弱 BC 细胞中信号蛋白的表达，但根据细胞类型和脂质效应器的不同，其程度也不同。这些信号蛋白与细胞凋亡和 BC 细胞迁移和侵袭性的减弱有关。此外，只有 DHA 减少了 MDA-MB-231 细胞在体外的迁移，而两种 LCPUFA 及其内源性大麻素均显著抑制了侵袭性。这一发现与所有处理均观察到的整合素 β3 表达减少以及 DHA 处理时 MMP-1 和 VEGF 减少一致。恶性细胞活力、迁移和侵袭的减弱表明，这些 LCPUFA 及其内源性大麻素在治疗乳腺癌方面具有潜在的辅助营养治疗用途。
