Caffeic acid phenethyl ester inhibits MDA-MB-231 cell proliferation in inflammatory microenvironment by suppressing glycolysis and lipid metabolism - 11/11/23
Abstract |
Caffeic acid phenethyl ester (CAPE) is one of the main active ingredients of propolis with good antitumor activities. However, the potential effects of CAPE on the glycolysis and lipid metabolism of tumor cells are unclear. Here, the anti-tumor effects of CAPE on MDA-MB-231 cells in an inflammatory microenvironment stimulated with lipopolysaccharide (LPS) were studied by estimating the inflammatory mediators and the key factors of glycolysis and lipid metabolism. The CAPE treatment obviously inhibited proliferation, migration, invasion, and angiogenesis, and the mitochondrial membrane potential was decreased in the LPS-stimulated MDA-MB-231 cells. Compared with the LPS group, pro-inflammatory mediators, including toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), NF-kappa-B inhibitor alpha (IκBα), interleukin (IL)-1β, and IL-6, as well as interleukin-1 receptor-associated kinase 4 (IRAK4), declined after the CAPE treatment. Additionally, CAPE significantly down-regulated the levels of glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3), and the key enzymes of glycolysis—hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA). Moreover, CAPE treatment decreased the levels of key lipid metabolism proteins, including acetyl coenzyme A carboxylase (ACC), fatty acid synthase (FASN), and free fatty acid (FFA)-transported-related protein CD36. After adding the glycolysis inhibitor 2-deoxy-D-glucose (2-DG), the inhibitory effects of CAPE on cell viability and migration were not significant when compared with the LPS group. In summary, the antitumor activity of CAPE in vitro was mainly via the modulation of the inflammatory mediators and the inhibition of key proteins and enzymes in glucose and lipid metabolism.
Le texte complet de cet article est disponible en PDF.Highlights |
• | CAPE exerted excellent antitumor activity in LPS-stimulated MDA-MB-231 cells. |
• | CAPE modulated inflammatory mediators in LPS-stimulated MDA-MB-231 cells. |
• | We firstly found CAPE suppressed glycolysis and lipid metabolism in LPS-stimulated MDA-MB-231 cells. |
Abbreviations : ACC, BC, CAPE, CCK-8, CD36, DMSO, ELISA, FAs, FASN, FBS, FFA, GLUT1, GLUT3, HK2, HUVECs, IL-1β, IL-6, IκBα, IRAK4, LDHA, LPS, NF-κB, PFK, PKM2, PVDF, RT-qPCR, SDS-PAGE, TLR4, TNBC, TNF-α, 2-DG
Keywords : Caffeic acid phenethyl ester, Antitumor activity, Glycolysis, Lipid metabolism, Lipopolysaccharide
Plan
Vol 168
Article 115766- décembre 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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