ArticleLipids in health and disease2019
4-cholesten-3-one decreases breast cancer cell viability and alters membrane raft-localized EGFR expression by reducing lipogenesis and enhancing LXR-dependent cholesterol transporters.
Article in Lipids in health and disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Intestinal Source Control of Lipid Metabolism by Enzyme-Probiotic Encapsulated, Spatiotemporal Crosslinked, and Small Intestine-Adhesive Hydrogel Microspheres.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting cholesterol metabolism: a promising therapy strategy for cancer.Acta pharmacologica Sinica · 2025Review
- Unraveling the causal pathway between phosphatidylinositol, metabolites, and metabolic syndrome: a Mendelian randomization study.Diabetology & metabolic syndrome · 2025Article
- Biochemical Pathways Delivering Distinct Glycosphingolipid Patterns in MDA-MB-231 and MCF-7 Breast Cancer Cells.Current issues in molecular biology · 2024Review
- The role of cholesterol and its oxidation products in tuberculosis pathogenesis.Immunometabolism (Cobham, Surrey) · 2024Review
- Oxysterols in Central and Peripheral Synaptic Communication.Advances in experimental medicine and biology · 2024Article
- Studies in the antiviral molecular mechanisms of 25-hydroxycholesterol: Disturbing cholesterol homeostasis and post-translational modification of proteins.European journal of pharmacology · 2022Review
- Preliminary screening of antioxidant and cytotoxic potential of green seaweed,Saudi journal of biological sciences · 2022Article
- Macrophage global metabolomics identifies cholestenone as host/pathogen cometabolite present in human Mycobacterium tuberculosis infection.The Journal of clinical investigation · 2022Article
- Isolation of the Cholesterol-Assimilating StrainFood science of animal resources · 2021Article
- Modulation of LXR signaling altered the dynamic activity of human colon adenocarcinoma cancer stem cells in vitro.Cancer cell international · 2021Article
- Natural Products Targeting Liver X Receptors or Farnesoid X Receptor.Frontiers in pharmacology · 2021Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe alteration of lipid metabolism in cancer cells is recognized as one of the most important metabolic hallmarks of cancer. Membrane rafts defined as plasma membrane microdomains enriched in cholesterol and sphingolipids serve as platforms for signaling regulation in cancer. The main purpose of this study was to evaluate the effect of the cholesterol metabolite, 4-cholesten-3-one, on lipid metabolism and membrane raft integrity in two breast cancer cell lines, MCF-7 and MDA-MB-231. Its ability to reduce cell viability and migration has also been investigated.
methodsRT-qPCR was performed to evaluate the expression of enzymes involved in lipogenesis and cholesterol synthesis, and ABCG1 and ABCA1 transporters involved in cholesterol efflux. Its effect on cell viability and migration was studied using the MTT assay, the wound healing assay and the Transwell migration assay, respectively. The effect of 4-cholesten-3-one on membrane rafts integrity was investigated by studying the protein expression of flotillin-2, a membrane raft marker, and raft-enriched EGFR by western blot.
resultsInterestingly, we found that 4-cholesten-3-one treatment decreased mRNA expression of different enzymes including ACC1, FASN, SCD1 and HMGCR. We further demonstrated that 4-cholesten-3-one increased the expression of ABCG1 and ABCA1. We also found that 4-cholesten-3-one decreased the viability of MCF-7 and MDA-MB-231 cells. This effect was neutralized after treatment with LXR inverse agonist or after LXRβ knockdown by siRNA. As a result, we also demonstrated that 4-cholesten-3-one disrupts membrane rafts and cell migration capacity.
conclusionOur results show that 4-cholesten-3-one exerts promising antitumor activity by altering LXR-dependent lipid metabolism in breast cancer cells without increasing lipogenesis.
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