ArticleLipids in health and disease2009
Gamma-linolenic acid inhibits both tumour cell cycle progression and angiogenesis in the orthotopic C6 glioma model through changes in VEGF, Flt1, ERK1/2, MMP2, cyclin D1, pRb, p53 and p27 protein expression.
Article in Lipids in health and disease, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 50 citations in OpenAlex.
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- Honokiol-Loaded Nanoemulsion for Glioblastoma Treatment: Statistical Optimization, Physicochemical Characterization, and an In Vitro Toxicity Assay.Pharmaceutics · 2023Article
- Gamma-Linolenic Acid (GLA) Protects against Ionizing Radiation-Induced Damage: An In Vitro and In Vivo Study.Biomolecules · 2022Article
- Inhibitory role of a smart nano-trifattyglyceride ofJournal of traditional and complementary medicine · 2021Article
- Evening Primrose (Antioxidants (Basel, Switzerland) · 2018Review
- PET Imaging with S-[Molecular imaging and biology · 2018Article
- Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid.The Journal of biological chemistry · 2016Article
- An evaluation of the anti-angiogenic effect of the Korean medicinal formula "Sa-mi-yeon-geon-tang" in vitro and in ovo.BMC complementary and alternative medicine · 2015Article
- Evening primrose oil and celecoxib inhibited pathological angiogenesis, inflammation, and oxidative stress in adjuvant-induced arthritis: novel role of angiopoietin-1.Inflammopharmacology · 2014Article
- Growth inhibitory effects of the Diruthenium-Ibuprofen compound, [Ru2Cl(Ibp) 4], in human glioma cells in vitro and in the rat C6 orthotopic glioma in vivo.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014Article
- Activation of NMDA receptor of glutamate influences MMP-2 activity and proliferation of glioma cells.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Article
- The influence of high glucose on the Cip/Kip family expression profiles in HRECs.Journal of molecular histology · 2013Article
- E series prostaglandins alter the proliferative, apoptotic and migratory properties of T98G human glioma cells in vitro.Lipids in health and disease · 2012Article
- Ethanol extract of Gleditsia sinensis thorn suppresses angiogenesis in vitro and in vivo.BMC complementary and alternative medicine · 2012Article
- Basic aspects of tumor cell fatty acid-regulated signaling and transcription factors.Cancer metastasis reviews · 2011Review
- Vascular endothelial growth factor increases permeability of the blood-tumor barrier via caveolae-mediated transcellular pathway.Journal of molecular neuroscience : MN · 2011Article
- Lipids, mitochondria and cell death: implications in neuro-oncology.Molecular neurobiology · 2010Review
- Cytotoxicity of unsaturated fatty acids in fresh human tumor explants: concentration thresholds and implications for clinical efficacy.Lipids in health and disease · 2009Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGamma-linolenic acid is a known inhibitor of tumour cell proliferation and migration in both in vitro and in vivo conditions. The aim of the present study was to determine the mechanisms by which gamma-linolenic acid (GLA) osmotic pump infusion alters glioma cell proliferation, and whether it affects cell cycle control and angiogenesis in the C6 glioma in vivo.
methodsEstablished C6 rat gliomas were treated for 14 days with 5 mM GLA in CSF or CSF alone. Tumour size was estimated, microvessel density (MVD) counted and protein and mRNA expression measured by immunohistochemistry, western blotting and RT-PCR.
resultsGLA caused a significant decrease in tumour size (75 +/- 8.8%) and reduced MVD by 44 +/- 5.4%. These changes were associated with reduced expression of vascular endothelial growth factor (VEGF) (71 +/- 16%) and the VEGF receptor Flt1 (57 +/- 5.8%) but not Flk1. Expression of ERK1/2 was also reduced by 27 +/- 7.7% and 31 +/- 8.7% respectively. mRNA expression of matrix metalloproteinase-2 (MMP2) was reduced by 35 +/- 6.8% and zymography showed MMP2 proteolytic activity was reduced by 32 +/- 8.5%. GLA altered the expression of several proteins involved in cell cycle control. pRb protein expression was decreased (62 +/- 18%) while E2F1 remained unchanged. Cyclin D1 protein expression was increased by 42 +/- 12% in the presence of GLA. The cyclin dependent kinase inhibitors p21 and p27 responded differently to GLA, p27 expression was increased (27 +/- 7.3%) while p21 remained unchanged. The expression of p53 was increased (44 +/- 16%) by GLA. Finally, the BrdU incorporation studies found a significant inhibition (32 +/- 11%) of BrdU incorporation into the tumour in vivo.
conclusionOverall the findings reported in the present study lend further support to the potential of GLA as an inhibitor of glioma cell proliferation in vivo and show it has direct effects upon cell cycle control and angiogenesis. These effects involve changes in protein expression of VEGF, Flt1, ERK1, ERK2, MMP2, Cyclin D1, pRb, p53 and p27. Combination therapy using drugs with other, complementary targets and GLA could lead to gains in treatment efficacy in this notoriously difficult to treat tumour.
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