The role of natural compounds in modulation of small extracellular vesicle biogenesis and lipid metabolism in cancer

Small extracellular vesicles (sEVs) are vesicles of 15-150 nm in diameter secreted by cells and contain biological compounds that aid in cell growth, proliferation, and communication. Over the years, their role in oncogenesis has become prominent, especially in modulating the tumor microenvironment, facilitating epithelial-mesenchymal transition, and promoting metastasis. These oncosomes serve as unique diagnostic markers that can be used to detect specific types of cancer. Their stable lipid bilayer is composed of various classes of lipids, including phosphatidylserine, sphingomyelin, ceramides, and sterols. Alterations in the lipid profile of sEVs have been found in various chronic diseases, including cancers, making them suitable biomarkers and therapeutic targets. Natural compounds (NCs) derived from plants and microbes exhibit antitumorigenic properties. They have been recognized in contemporary medicine for their capacity to modulate sEV synthesis, secretion, and composition. However, there is limited research on the effects of NCs on the lipid panel of extracellular vesicles, as most studies have focused on proteins and microRNAs. Considering that NCs can influence key regulatory enzymes involved in lipogenesis and degradation, this suggests a potential impact on the lipid composition of sEVs. Therefore, we summarized the direct effects of NCs on sEVs and lipid-related enzymes, highlighting the potential for natural compound-mediated lipid modulation in sEVs.