Dietary alpha-linolenic acid reduces COX-2 expression and induces apoptosis of hepatoma cells.

Fatty acid synthetase (FAS) is overexpressed in various tumor tissues, and its inhibition and/or malonyl-CoA accumulation have been correlated to apoptosis of tumor cells. It is widely recognized that both omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) depress FAS expression in liver, although epidemiological and experimental reports attribute antitumor properties only to omega-3 PUFA. Therefore, we investigated whether lipogenic gene expression in tumor cells is differently regulated by omega-6 and omega-3 PUFAs. Morris hepatoma 3924A cells were implanted subcutaneously in the hind legs of ACI/T rats preconditioned with high-lipid diets enriched with linoleic acid or alpha-linolenic acid. Both-high lipid diets depressed the expression of FAS and acetyl-CoA carboxylase in tumor tissue, this effect correlating with a decrease in the mRNA level of their common sterol regulatory element binding protein-1 transcription factor. Hepatoma cells grown in rats on either diet did not accumulate malonyl-CoA. Apoptosis of hepatoma cells was induced by the alpha-linolenic acid-enriched diet but not by the linoleic acid-enriched diet. Therefore, in this experimental model, apoptosis is apparently independent of the inhibition of fatty acid synthesis and of malonyl-CoA cytotoxicity. Conversely, it was observed that apoptosis induced by the alpha-linolenic acid-enriched diet correlated with a decrease in arachidonate content in hepatoma cells and decreased cyclooxygenase-2 expression.

• Publication year

  2004

• Venue

  Journal of Lipid Research

• Publication date

  2004-02-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1194/JLR.M300396-JLR200PMID 14563831
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Inhibited proliferation of cyclooxygenase-2 expressing human hepatoma cells by NS-398, a selective COX-2 inhibitor.

  2003cited by this paper
• Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion.

  2003cited by this paper
• Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c.

  2003cited by this paper
• Effects of dietary linseed, evening primrose or fish oils on fatty acid and prostaglandin E2 contents in the rat livers and 7,12-dimethylbenz[a]anthracene-induced tumours.

  2003cited by this paper
• Immunohistochemical expression and prognostic significance of FAS and GLUT1 in bladder carcinoma.

  2003cited by this paper
• Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion

  2003cited by this paper
• In vitro studies on the relationship between polyunsaturated fatty acids and cancer: tumour or tissue specific effects?

  2002cited by this paper
• Effect of nimesulide on proliferation and apoptosis of human hepatoma SMMC-7721 cells.

  2002cited by this paper
• CCAAT/enhancer-binding proteins: structure, function and regulation.

  2002cited by this paper
• Activation of fatty acid synthesis during neoplastic transformation: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase.

  2002cited by this paper
• Suppression of fatty acid synthase promoter by polyunsaturated fatty acids.

  2002cited by this paper
• Housekeeping gene variability in normal and carcinomatous colorectal and liver tissues: applications in pharmacogenomic gene expression studies.

  2002cited by this paper
• Many actions of cyclooxygenase‐2 in cellular dynamics and in cancer

  2002cited by this paper
• Proapoptotic and antiproliferative potential of selective cyclooxygenase‐2 inhibitors in human liver tumor cells

  2002cited by this paper
• Significance of cyclooxygenase-2 expression in human primary hepatocellular carcinoma.

  2002cited by this paper
• Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer

  2002cited by this paper
• Androgens stimulate lipogenic gene expression in prostate cancer cells by activation of the sterol regulatory element-binding protein cleavage activating protein/sterol regulatory element-binding protein pathway.

  2001cited by this paper
• The Transcription Factor C/EBPβ Is Essential for Inducible Expression of the cox-2 Gene in Macrophages but Not in Fibroblasts*

  2001cited by this paper
• The induction of cyclooxygenase-2 mRNA in macrophages is biphasic and requires both CCAAT enhancer-binding protein beta (C/EBP beta ) and C/EBP delta transcription factors.

  2001cited by this paper
• The Induction of Cyclooxygenase-2 mRNA in Macrophages Is Biphasic and Requires both CCAAT Enhancer-binding protein β (C/EBPβ) and C/EBPδ Transcription Factors*

  2001cited by this paper
• Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor, NS-398.

  2001cited by this paper
• Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53.

  2001cited by this paper
• Synthesis and antitumor activity of an inhibitor of fatty acid synthase

  2000cited by this paper
• Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts.

  2000cited by this paper
• Stimulation of tumor-associated fatty acid synthase expression by growth factor activation of the sterol regulatory element-binding protein pathway

  2000cited by this paper
• Cyclooxygenase-2 and carcinogenesis.

  2000cited by this paper
• Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia.

  2000cited by this paper
• Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization.

  1999cited by this paper
• Sterol Regulatory Element Binding Protein-1 Expression Is Suppressed by Dietary Polyunsaturated Fatty Acids

  1999cited by this paper
• Expression of cyclooxygenase‐2 in human hepatocellular carcinoma: Relevance to tumor dedifferentiation

  1999cited by this paper
• Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi.

  1999cited by this paper
• Cyclooxygenase-2 expression in hepatocellular carcinoma.

  1999cited by this paper
• A novel splicing isoform of mouse sterol regulatory element-binding protein-1 (SREBP-1).

  1999cited by this paper
• Dietary fat and carcinogenesis.

  1999cited by this paper
• Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: Effects on proliferation and apoptosis

  1998cited by this paper
• Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines.

  1998cited by this paper
• Polyunsaturated Fatty Acids Decrease Expression of Promoters with Sterol Regulatory Elements by Decreasing Levels of Mature Sterol Regulatory Element-binding Protein*

  1998cited by this paper
• Fatty acid synthase expression in endometrial carcinoma

  1998cited by this paper
• Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia.

  1997cited by this paper
• Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs.

  1997cited by this paper
• Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells.

  1996cited by this paper
• Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein.

  1996cited by this paper
• Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients

  1996cited by this paper
• Rapid method for the separation and detection of tissue short-chain coenzyme A esters by reversed-phase high-performance liquid chromatography.

  1995cited by this paper
• Generation of mutagens during arachidonic acid metabolism

  1994cited by this paper
• A revised sequence of the rat c/ebp gene.

  1994cited by this paper
• Cloning, sequencing, and expression of a cDNA encoding rat liver carnitine palmitoyltransferase I. Direct evidence that a single polypeptide is involved in inhibitor interaction and catalytic function.

  1993cited by this paper
• ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation

  1993cited by this paper
• Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression.

  1993cited by this paper
• Kinetics of the inhibition of tumour growth in mice by eicosapentaenoic acid-reversal by linoleic acid.

  1993cited by this paper
• Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor.

  1992cited by this paper
• Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation

  1992cited by this paper
• The effect of omega-6 and omega-3 fatty acids on 3H-thymidine incorporation in hepatoma 7288CTC perfused in situ.

  1992cited by this paper
• Molecular characterization of transcription factors that bind to the cAMP responsive region of the substance P precursor gene. cDNA cloning of a novel C/EBP-related factor.

  1991cited by this paper
• Effect of diets high in omega-3 and omega-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis.

  1991cited by this paper
• Effects of dietary perilla oil, soybean oil and safflower oil on 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethyl-hydrazine (DMH)-induced mammary gland and colon carcinogenesis in female SD rats.

  1990cited by this paper
• Rat ATP citrate-lyase. Molecular cloning and sequence analysis of a full-length cDNA and mRNA abundance as a function of diet, organ, and age.

  1990cited by this paper
• LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein.

  1990cited by this paper
• Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase.

  1989cited by this paper
• Structure of the coding sequence and primary amino acid sequence of acetyl-coenzyme A carboxylase.

  1988cited by this paper
• Complete nucleotide sequence of cDNA and predicted amino acid sequence of rat acyl-CoA oxidase.

  1987cited by this paper
• Effect of omega-3 fatty acids on growth of a rat mammary tumor.

  1984cited by this paper
• Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.

  1979cited by this paper
• A simple method for the isolation and purification of total lipides from animal tissues.

  1957cited by this paper
• The FASEB Journal express article 10.1096/fj.01-0158fje. Published online July 9, 2001. Contribution of cyclooxygenase-2 to liver regeneration after partial hepatectomy

  year unknowncited by this paper

• Role of gut microbiota in the pathogenesis of castration-resistant prostate cancer: a comprehensive study using sequencing and animal models

  2024cites this paper
• The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer

  2023cites this paper
• Impact of Omega 3 on the Genotoxicity of Irinotecan on Bone Marrow and Spleen of Rats: in-vivo Study

  2023cites this paper
• A cuproptosis-related lncRNAs risk model to predict prognosis and guide immunotherapy for lung adenocarcinoma

  2023cites this paper
• Physiological and Pathological Considerations for the Use of Flaxseed as a Therapeutic Dietary Strategy

  2023cites this paper
• Protective Effect of Alpha-Linolenic Acid on Human Oral Squamous Cell Carcinoma Metastasis and Apoptotic Cell Death

  2023cites this paper
• Uncovering the Mechanisms of Active Components from Toad Venom against Hepatocellular Carcinoma Using Untargeted Metabolomics

  2022cites this paper
• Emergence of nutrigenomics and dietary components as a complementary therapy in cancer prevention

  2022cites this paper
• Cancer diets for cancer patients: Lessons from mouse studies and new insights from the study of fatty acid metabolism in tumors.

  2020cites this paper
• Chinese herbal medicine mixture 919 syrup alleviates nonalcoholic fatty liver disease in rats by inhibiting the NF-κB pathway.

  2020cites this paper
• Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer

  2018cites this paper
• Molecular basis of vascular damage caused by cigarette smoke exposure and a new approach to the treatment: Alpha-linolenic acid.

  2018cites this paper
• Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

  2018cites this paper
• Alpha linolenic acid decreases apoptosis and oxidized phospholipids in cardiomyocytes during ischemia/reperfusion

  2017cites this paper
• Dietary α-linolenic acid affects lipid metabolism and tissue fatty acid profile and induces apoptosis in intraperitoneal adipose tissue of juvenile grass carp (Ctenopharyngodon idella)

  2017cites this paper
• Down-regulation of NF-κB expression by n-3 fatty acid-rich linseed oil is modulated by PPARγ activation, eicosanoid cascade and secretion of cytokines by macrophages in rats fed partially hydrogenated vegetable fat

  2017cites this paper
• How plausible is the use of dietary n-3 PUFA in the adjuvant therapy of cancer?

  2016cites this paper
• Molecular Mechanisms for the Modulation of Selected Inflammatory Markers by Dietary Rice Bran Oil in Rats Fed Partially Hydrogenated Vegetable Fat

  2016cites this paper
• Effet anti-tumoral de l'acide docosahexaénoïque : implication des microARNs et du TNFalpha

  2015cites this paper
• Distinct genotype-dependent differences in transcriptome responses in humans exposed to environmental carcinogens.

  2015cites this paper
• Emulsions Made of Oils from Seeds of GM Flax Protect V79 Cells against Oxidative Stress

  2015cites this paper
• Integrative Genomic Signatures Of Hepatocellular Carcinoma Derived from Nonalcoholic Fatty Liver Disease

  2015cites this paper
• Chemical Constituents of Cycas sancti-lasallei.

  2015cites this paper
• α-Linolenic acid: nutraceutical, pharmacological and toxicological evaluation.

  2014cites this paper
• Lipid Emulsions Differentially Affect LPS-Induced Acute Monocytes Inflammation: In Vitro Effects on Membrane Remodeling and Cell Viability

  2014cites this paper
• ω-3 Polyunsaturated fatty acids and their metabolites as inhibitors of mammalian tumorigenesis

  2014cites this paper
• Long term consumption of flaxseed enriched diet decreased ovarian cancer incidence and prostaglandin E₂in hens.

  2013cites this paper
• Current Evidence Linking Polyunsaturated Fatty Acids with Cancer Risk and Progression

  2013influential citation
• Omega-3 Fatty Acids Inhibit Tumor Growth in a Rat Model of Bladder Cancer

  2013cites this paper
• Selection of nutraceutical compounds as COX inhibitors by molecular topology

  2013cites this paper
• What is more damaging to vascular endothelial function: Diabetes, age, high BMI, or all of the above?

  2013cites this paper
• CoQ10 and Endothelial Function in Asians from Korea compared to Asians born in the United States and US Born Caucasians

  2013cites this paper
• Prevention of Familial Adenomatous Polyp Development in APCmin Mice and Azoxymethane-Induced Colon Carcinogenesis in F344 Rats by ω-3 Fatty Acid Rich Perilla Oil

  2013cites this paper
• Association of cyclooxygenase 2 single-nucleotide polymorphisms and hepatocellular carcinoma in Taiwan.

  2012cites this paper
• Palmitic and linoleic acids induce ER stress and apoptosis in hepatoma cells

  2012cites this paper
• Szív, tumor és idegsejtek fókuszált miRNS és mRNS expressziós analízise Ph.D értekezés

  2012cites this paper
• Assessment of nutritional status and analytical methods.

  2012cites this paper
• The effect of coenzyme Q10 on endothelial function in a young population

  2012cites this paper
• Beta-eleostearic acid induce apoptosis in T24 human bladder cancer cells through reactive oxygen species (ROS)-mediated pathway.

  2012cites this paper
• Eicosapentaenoic Acid Demethylates a Single CpG That Mediates Expression of Tumor Suppressor CCAAT/Enhancer-binding Protein δ in U937 Leukemia Cells*

  2011cites this paper
• Efectos de los ácidos grasos omega 3 y otros suplementos alimenticios en procesos patológicos relacionados con la tercera edad

  2011cites this paper
• Docosahexaenoic acid reverts resistance to UV-induced apoptosis in human keratinocytes: involvement of COX-2 and HuR.

  2011cites this paper
• Dietary n-3 polyunsaturated fatty acids and the paradox of their health benefits and potential harmful effects.

  2011cites this paper
• Polyunsaturated fatty acids reduce Fatty Acid Synthase and Hydroxy-Methyl-Glutaryl CoA-Reductase gene expression and promote apoptosis in HepG2 cell line

  2011cites this paper
• The Health Promoting Properties of the Conjugated Isomers of α-Linolenic Acid

  2011influential citation
• Genetic and Environmental Factors Suggest that Dietary Fatty Acid Content, Lipid Metabolism, and Bone Properties are Key Regulators of Myeloid Progenitor Cell Frequency

  2010cites this paper
• Resolution of Adipose Tissue Inflammation

  2010cites this paper
• Resolvins, protectins and other lipid mediators in obesity-associated inflammatory disorders

  2010cites this paper
• Lipids in Health and Disease

  2009cites this paper
• Contrasting Effects of n-3 and n-6 Fatty Acids on Cyclooxygenase-2 in Model Systems for Arthritis

  2009cites this paper
• Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer

  2009cites this paper
• Efectos protectores de los Ácidos grasos Omega-3 en el hígado y el tejido adiposo

  2009cites this paper
• The relationship between genetic and environmental factors La relazione tra fattori genetici e ambientali

  2008cites this paper
• Lipids in Health and Disease

  2008cites this paper
• COX-2 expression in cystic kidneys is dependent on dietary n-3 fatty acid composition.

  2007influential citation
• Regulation of Cyclooxygenase-2 by Environmental and Dietary Factors

  2007cites this paper
• Growth inhibition and induction of early apoptosis by arenicolsterol A, a novel cytotoxic enolic sulphated sterol from the marine annelid, Arenicola cristata

  2007cites this paper
• Immunostimulant dérivé d'algue et agent anti-inflammatoire dérivé d'algue

  2007cites this paper
• Alpha-linolenic acid attenuates high glucose-induced apoptosis in cultured human umbilical vein endothelial cells via PI3K/Akt/eNOS pathway.

  2007cites this paper
• Basic nutritional investigation -Linolenic acid attenuates high glucose-induced apoptosis in cultured human umbilical vein endothelial cells via PI3K/Akt/eNOS pathway

  2007cites this paper
• n-3 fatty acids and gene expression.

  2006cites this paper
• n3 Fatty acids and gene expression 1-4

  2006cites this paper
• The influence of dietary compounds like polyunsaturated fatty acids in colon cancer development: role of Cox-2 and PPARs

  2006cites this paper
• Induction of apoptosis in K562/ADM cells by gamma-linolenic acid involves lipid peroxidation and activation of caspase-3.

  2006cites this paper
• Conjugated linoleic acid attenuates cyclooxygenase-2 transcriptional activity via an anti-AP-1 mechanism in MCF-7 breast cancer cells.

  2006cites this paper
• Toxicity of a soybean oil emulsion on human lymphocytes and neutrophils.

  2006cites this paper
• Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators: protectin D1 and 17S‐hydroxy‐DHA

  2006cites this paper
• Dietary modulation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced adrenal toxicity in female Sprague-Dawley rats.

  2005cites this paper
• Dietary PUFA modulate the expression of proliferation and differentiation markers in Morris 3924A hepatoma cells.

  2005cites this paper
• Lipids in Health and Disease Modulation Peroxisome Proliferators Activated Receptor Alpha (ppar Α) and Acyl Coenzyme A: Cholesterol Acyltransferase1 (acat1) Gene Expression by Fatty Acids in Foam Cell

  year unknowncites this paper