In recent years, Docosahexaenoic acid has been shown to have anti-tumoral activity and is being tested for breast cancer treatments. However, its anti-cancer mechanisms remain unclear. The tumor microenvironment has an essential role in cancer progression and exosomes have been identified as essential mediators in promoting angiogenesis, but there is little knowledge on their exact contribution or whether they can modulate Docosahexaenoic acid anticancer activity. Here, human breast cancer cell lines were treated with Docosahexaenoic acid to investigate the role of exosomes in Docosahexaenoic acid-mediated anticancer activity and co-cultured with human endothelial cells to explore its anti-angiogenesis role. The results showed increased exosome secretion with microRNAs altered levels after treatment of cancer cells. Those mostly overexpressed were identified to have anti-cancer properties and were overexpressed also in exosomes of different Docosahexaenoic acid-treated breast cancer cell lines, but not in normal breast cells. Finally, co-culture of Docosahexaenoic acid-treated breast cancer cells with endothelial cells induced increased levels of the same microRNAs in endothelial cells, in which they reduced pro-angiogenic genes expression and inhibited tube formation. Additionally, the anti-angiogenic activity could be reversed with the knockdown of genes related to exosome secretion. Overall, the researchers demonstrate that Docosahexaenoic acid treatment disrupts angiogenesis capabilities of breast cancer cells through the modulation of microRNAs rich exosomes, which could lead to new anti-cancer targets and further validate Docosahexaenoic acid for cancer treatment.
Exosome-mediated microRNA signaling from breast cancer cells is altered by the anti-angiogenesis agent docosahexaenoic acid (DHA)
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