ArticleInternational journal of molecular sciences2022
Resveratrol Affects Sphingolipid Metabolism in A549 Lung Adenocarcinoma Cells.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Curcumin as a ceramide metabolism-targeting agent: Molecular mechanisms and therapeutic implications in cancer.Molecular biology reports · 2026Review
- Disruption of sphingolipid metabolism triggers lung vascular inflammation and aging-like changes under hypoxia through VDAC1-mediated mitochondrial DNA release.Apoptosis : an international journal on programmed cell death · 2026Article
- Molecular Mechanism and Research Progress of Sphingolipid Metabolism in Regulating Radiation-induced Apoptosis Using Pan-cancer Analysis.Current cancer drug targets · 2026Review
- Functional combination of resveratrol and midostaurin induces cytotoxicity to overcome acquired midostaurin resistance in FLT3-ITD expressing acute myeloid leukemia cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Untargeted LC-IMS-qToF-MS-Based Lipidomics Approach to Evaluate the Effect of a Polyphenol-Rich Beverage on Human Lipid Profiles.International journal of molecular sciences · 2025Article
- Bidirectional two-sample Mendelian randomization reveals causal link between genetic blood metabolites and tuberculosis.AMB Express · 2025Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- Exploring the effect of epigallocatechin gallate on non small cell lung cancer.International journal of biochemistry and molecular biology · 2024Article
- Sphingolipid Levels and Signaling via Resveratrol and Antioxidant Actions in Cardiometabolic Risk and Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Mechanisms of Arachidonic Acid In Vitro Tumoricidal Impact.Molecules (Basel, Switzerland) · 2023Article
- Antioxidant and Cytotoxic Activity of New Polyphenolic Derivatives of Quinazolin-4(3H)-one: Synthesis and In Vitro Activities Evaluation.Pharmaceutics · 2022Article
- Effect of Quercetin and Fingolimod, Alone or in Combination, on the Sphingolipid Metabolism in HepG2 Cells.International journal of molecular sciences · 2022Article
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
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Authors and funding
11 authors at 6 institutions in 2 countries.
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Abstract
Resveratrol is a naturally occurring polyphenol which has various beneficial effects, such as anti-inflammatory, anti-tumor, anti-aging, antioxidant, and neuroprotective effects, among others. The anti-cancer activity of resveratrol has been related to alterations in sphingolipid metabolism. We analyzed the effect of resveratrol on the enzymes responsible for accumulation of the two sphingolipids with highest functional activity-apoptosis promoting ceramide (CER) and proliferation-stimulating sphingosine-1-phosphate (S1P)-in human lung adenocarcinoma A549 cells. Resveratrol treatment induced an increase in CER and sphingosine (SPH) and a decrease in sphingomyelin (SM) and S1P. Our results showed that the most common mode of CER accumulation, through sphingomyelinase-induced hydrolysis of SM, was not responsible for a CER increase despite the reduction in SM in A549 plasma membranes. However, both the activity and the expression of CER synthase 6 were upregulated in resveratrol-treated cells, implying that CER was accumulated as a result of stimulated de novo synthesis. Furthermore, the enzyme responsible for CER hydrolysis, alkaline ceramidase, was not altered, suggesting that it was not related to changes in the CER level. The enzyme maintaining the balance between apoptosis and proliferation, sphingosine kinase 1 (SK1), was downregulated, and its expression was reduced, resulting in a decrease in S1P levels in resveratrol-treated lung adenocarcinoma cells. In addition, incubation of resveratrol-treated A549 cells with the SK1 inhibitors DMS and fingolimod additionally downregulated SK1 without affecting its expression. The present studies provide information concerning the biochemical processes underlying the influence of resveratrol on sphingolipid metabolism in A549 lung cancer cells and reveal possibilities for combined use of polyphenols with specific anti-proliferative agents that could serve as the basis for the development of complex therapeutic strategies.
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