ArticleMolecular cancer2013
Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
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Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression.Frontiers in oncology · 2022Pooled it
- Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: a systematic review and meta-analysis.BMC nephrology · 2021Pooled it
- JAB1/CRL4B complex represses PPARG/ACSL5 expression to promote breast tumorigenesis.Cell death and differentiation · 2026Article
- Cholesterol as a metabolic integrator of oncogenic signaling, immune evasion, and therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Fatty Acids in Cancer Therapy: Chemical Conjugates, Nanocarriers, and Therapeutic Opportunities.Molecules (Basel, Switzerland) · 2026Review
- Inflammation- and resolution-programmed myeloid circuits govern therapeutic resistance in epithelial and mesenchymal triple-negative breast cancer.The Journal of clinical investigation · 2026Article
- Integrative analyses of dicarbonyls and advanced glycation end-products with multiomic profiles across tissue, plasma and stool samples reveal methylglyoxal accumulation in colon cancer.Free radical biology & medicine · 2026Article
- Nutritional Modulation of Impaired Blood-Brain Barrier Integrity and Function in Major Depression.International journal of molecular sciences · 2025Review
- Construction of a prognostic signature for breast cancer based on genes involved in unsaturated fatty acid biosynthesis.Translational cancer research · 2025Article
- Omega-3 fatty acids: molecular weapons against chemoresistance in breast cancer.Cellular & molecular biology letters · 2025Review
- Steroidal saponins: Natural compounds with the potential to reverse tumor drug resistance (Review).Oncology letters · 2024Review
- Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens.Human cell · 2024Article
- Omega-3 Polyunsaturated Fatty Acids and Blood-Brain Barrier Integrity in Major Depressive Disorder: Restoring Balance for Neuroinflammation and Neuroprotection.The Yale journal of biology and medicine · 2024Review
- Dual Inhibitors of P-gp and Carbonic Anhydrase XII (hCA XII) against Tumor Multidrug Resistance with Piperazine Scaffold.Molecules (Basel, Switzerland) · 2024Article
- Understanding the Role of Polyunsaturated Fatty Acids in the Development and Prevention of Cancer.Cancer treatment and research · 2024Review
- p140Cap modulates the mevalonate pathway decreasing cell migration and enhancing drug sensitivity in breast cancer cells.Cell death & disease · 2023Article
- Targeting dysregulated lipid metabolism in the tumor microenvironment.Archives of pharmacal research · 2023Review
- Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications.International journal of molecular sciences · 2023Article
- Effect of Polyunsaturated Fatty Acids on Temozolomide Drug-Sensitive and Drug-Resistant Glioblastoma Cells.Biomedicines · 2023Article
- Protein degradation: expanding the toolbox to restrain cancer drug resistance.Journal of hematology & oncology · 2023Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the response to chemotherapy in multidrug resistant (MDR) tumors.
methodsWe studied the effect of omega 3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in human chemosensitive colon cancer HT29 cells and in their MDR counterpart, HT29-dx cells.
resultsMDR cells, which overexpressed Pgp and MRP1, had a dysregulated cholesterol metabolism, due to the lower expression of ubiquitin E3 ligase Trc8: this produced lower ubiquitination rate of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoAR), higher cholesterol synthesis, higher cholesterol content in MDR cells. We found that DHA and EPA re-activated Trc8 E3 ligase in MDR cells, restored the ubiquitination rate of HMGCoAR to levels comparable with chemosensitive cells, reduced the cholesterol synthesis and incorporation in DRMs. Omega 3 PUFAs were incorporated in whole lipids as well as in DRMs of MDR cells, and altered the lipid composition of these compartments. They reduced the amount of Pgp and MRP1 contained in DRMs, decreased the transporters activity, restored the antitumor effects of different chemotherapeutic drugs, restored a proper tumor-immune system recognition in response to chemotherapy in MDR cells.
conclusionsOur work describes a new biochemical effect of omega 3 PUFAs, which can be useful to overcome chemoresistance in MDR colon cancer cells.
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