ArticlePloS one2015
Sphingosine Kinase 2 and Ceramide Transport as Key Targets of the Natural Flavonoid Luteolin to Induce Apoptosis in Colon Cancer Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
- Plant bioactive compounds driven microRNAs (miRNAs): A potential source and novel strategy targeting gene and cancer therapeutics.Non-coding RNA research · 2024Article
- Role of Luteolin as Potential New Therapeutic Option for Patients with Glioblastoma through Regulation of Sphingolipid Rheostat.International journal of molecular sciences · 2023Article
- Antiviral Activity of Luteolin against Pseudorabies Virus In Vitro and In Vivo.Animals : an open access journal from MDPI · 2023Article
- Yeast as a Model to Find New Drugs and Drug Targets forInternational journal of molecular sciences · 2022Review
- Recent updates on anticancer mechanisms of polyphenols.Frontiers in cell and developmental biology · 2022Review
- Molecular Targets and Mechanisms ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- A Dansyl-Modified Sphingosine Kinase Inhibitor DPF-543 Enhanced De Novo Ceramide Generation.International journal of molecular sciences · 2021Article
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- The Impact of Whole Grain Intake on Gastrointestinal Tumors: A Focus on Colorectal, Gastric, and Esophageal Cancers.Nutrients · 2020Review
- Flavonoids as Potential Drugs forGenes · 2020Article
- Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer.Molecules (Basel, Switzerland) · 2020Review
- Sphingosine-1-Phosphate in the Tumor Microenvironment: A Signaling Hub Regulating Cancer Hallmarks.Cells · 2020Review
- Luteolin suppresses colorectal cancer cell metastasis via regulation of the miR‑384/pleiotrophin axis.Oncology reports · 2019Article
- Treatment implications of natural compounds targeting lipid metabolism in nonalcoholic fatty liver disease, obesity and cancer.International journal of biological sciences · 2019Review
- Review
- Chloroform fraction ofOncology letters · 2018Article
- Testosterone regulates the expression and functional activity of sphingosine-1-phosphate receptors in the rat corpus cavernosum.Journal of cellular and molecular medicine · 2018Article
- Liposome encapsulated luteolin showed enhanced antitumor efficacy to colorectal carcinoma.Molecular medicine reports · 2018Article
- S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling.Mediators of inflammation · 2017Review
- Natural Polyphenols for Prevention and Treatment of Cancer.Nutrients · 2016Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The plant flavonoid luteolin exhibits different biological effects, including anticancer properties. Little is known on the molecular mechanisms underlying its actions in colorectal cancer (CRC). Here we investigated the effects of luteolin on colon cancer cells, focusing on the balance between ceramide and sphingosine-1-phosphate (S1P), two sphingoid mediators with opposite roles on cell fate. Using cultured cells, we found that physiological concentrations of luteolin induce the elevation of ceramide, followed by apoptotic death of colon cancer cells, but not of differentiated enterocytes. Pulse studies revealed that luteolin inhibits ceramide anabolism to complex sphingolipids. Further experiments led us to demonstrate that luteolin induces an alteration of the endoplasmic reticulum (ER)-Golgi flow of ceramide, pivotal to its metabolic processing to complex sphingolipids. We report that luteolin exerts its action by inhibiting both Akt activation, and sphingosine kinase (SphK) 2, with the consequent reduction of S1P, an Akt stimulator. S1P administration protected colon cancer cells from luteolin-induced apoptosis, most likely by an intracellular, receptor-independent mechanism. Overall this study reveals for the first time that the dietary flavonoid luteolin exerts toxic effects on colon cancer cells by inhibiting both S1P biosynthesis and ceramide traffic, suggesting its dietary introduction/supplementation as a potential strategy to improve existing treatments in CRC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.