Oleamide, a sleep-inducing compound: Effects on Ion channels and cancer

Primary fatty acid amides (PFAMs) are interesting lipid-derived signaling molecules with wide-ranging actions, including bioelectric. In this perspective, we evaluate a possible triangular relationship: PFAMs-ion channels-cancer. The primary emphasis is on oleamide and its metabolic associate, oleic acid (OA). As ion channels, we have focused on voltage-gated sodium channels (VGSCs) and voltage-gated and inward rectifier potassium channels in a variety of cell types, including cancer cells. As cancers, we evaluate the evidence for breast and colorectal cancers. Cis-oleamide blocked VGSCs and potassium channels. In parallel, but not always concurrently, oleamide has been shown to produce antiproliferative and anti-invasive effects, consistent with the known control of these cellular behaviors by potassium channels and VGSCs, respectively. Importantly, there is also evidence that oleamide can potentiate chemotherapy. In contrast to oleamide, the effects of OA on the ion channels of interest and, correspondingly, cancer cell behaviors are much less consistent. The perspective is concluded with three short sections. First, we outline the actions of some other PFAMs, especially anandamide and linoleamide. Second, we give an overview of some other targets that have been associated with oleamide, especially cannabinoid receptors and gap junctions. Finally, we cover the anticancer effects of oleamide on some other neoplasms.