Arachidonic Acid Attenuates Cell Proliferation, Migration and Viability by a Mechanism Independent on Calcium Entry

Abstract

Arachidonic acid (AA) is a phospholipase A2 metabolite that has been reported to mediate a plethora of cellular mechanisms involved in healthy and pathological states such as platelet aggregation, lymphocyte activation, and tissue inflammation. AA has been described to activate Ca2+ entry through the arachidonate-regulated Ca2+-selective channels (ARC channels). Here, the analysis of the changes in the intracellular Ca2+ homeostasis revealed that, despite MDA-MB-231 cells expressing the ARC channel components Orai1, Orai3, and STIM1, AA does not evoke Ca2+ entry in these cells. We observed that AA evokes Ca2+ entry in MDA-MB-231 cells transiently expressing ARC channels. Nevertheless, MDA-MB-231 cell treatment with AA reduces cell proliferation and migration while inducing cell death through apoptosis. The latter mostly likely occurs via mitochondria membrane depolarization and the activation of caspases-3, -8, and -9. Altogether, our results indicate that AA exerts anti-tumoral effects on MDA-MB-231 cells, without having any effect on non-tumoral breast epithelial cells, by a mechanism that is independent on the activation of Ca2+ influx via ARC channels.

Metabolism-associated Molecular Classification of Cervical Cancer

“…Glycolysis/gluconeogenesis can in uence tumour recurrence and has been proven in previous studies to be an independent prognostic factor for tumour recurrence in advanced CESC patients treated with de nitive chemoradiotherapy (Hong et al, 2016). Furthermore, we also discovered that the arachidonic acid metabolism module was related to cell proliferation using the GSVA algorithm and that this might attenuate cell proliferation via a mechanism independent of calcium entry, thereby contributing to poor prognosis (Cantonero et al, 2020).…”

The Active Components of Sunflower (Helianthus annuus L.) Calathide and the Effects on Urate Nephropathy Based on COX-2/PGE2 Signaling Pathway and the Urate Transporter URAT1, ABCG2, and GLUT9

“…Due to the limited conditions, four representative compounds that may be of value for further study were preliminarily speculated based on the publications and the UPLC-MS/MS results in the current work. It has been evidenced that Arachidonic acid affects platelets function (52), cell cycle dynamics (53), and renal microvascular function related to its cytochrome P450 metabolites (54,55). Chlorogenic acid has been reported to have antioxidant and anti-inflammatory properties in the liver and kidney, and studies demonstrate that it is able to attenuate the kidney injury via a signaling pathway (56)(57)(58)(59).…”

Role of Orai3 in the Pathophysiology of Cancer

“…However, in these cells, Orai1 is the predominant constituent of the channels mediating SOCE [ 31 , 42 ] which challenged the relevance of Orai3 in Ca 2+ homeostasis. Interestingly, while these cells express all the components of the ARC channels, i.e., Orai1, Orai3, and STIM1, stimulation with AA was unable to induce Ca 2+ influx but, rather, attenuated the ability of MDA-MB-231 cells to migrate and proliferate by inducing disruption of the mitochondrial membrane potential and the activation of apoptosis [ 43 ]. Nevertheless, cell stimulation with 2-APB revealed the presence of functional Orai3 channels in MDA-MB-231 cells, and Orai3 knockdown unveiled that Orai3 protects the cells against the harmful effects of AA [ 43 ].…”