Lipoxins, resolvins, protectins, maresins and nitrolipids, and their clinical implications with specific reference to cancer: part I

References

• Wylie CM. The definition and measurement of health and disease. Public Health Rep. 85, 100–104 (1970).
   Google Scholar
• Lopez A, Mathers C, Ezzati M, Jamison D, Murray C. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367, 1714–1717 (2006).
   Google Scholar
• Das UN. Hypertension as a low‑grade systemic inflammatory condition that has its origins in the perinatal period. J. Assoc. Physicians India 54, 133–142 (2006).
   Google Scholar
• Luc G, Bard J‑M, Juhan‑Vague I et al. C‑reactive protein, interleukins‑6, and fibrinogen as predictors of coronary heart disease. The PRIME study. Arterioscler. Thromb. Vasc. Biol. 23, 1255–1261 (2003).
   Google Scholar
• Das UN. Is obesity an inflammatory condition? Nutrition 17, 953–966 (2001). First manuscript proposing that obesity could be a low-grade systemic inflammatory condition.
   Google Scholar
• Das UN. Is metabolic syndrome X an inflammatory condition? Exp. Biol. Med. (Maywood) 227, 989–997 (2002).
   Google Scholar
• Ridker PM, Burning JE, Cook NR, Rifai N. C‑reactive protein, the metabolic syndrome, and risk of incident cardiovascular events. Circulation 107, 391–397 (2003).
   Google Scholar
• Das UN. Is metabolic syndrome X a disorder of the brain with the initiation of low‑grade systemic inflammatory events during the perinatal period? J. Nutr. Biochem. 18, 701–713 (2007). Documents the existing evidence that Type 2 diabetes could be a disorder of the brain. It was also suggested that Type 2 diabetes may be due to a dysfunction of the hypothalamus.
   Google Scholar
• Das UN. Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer’s disease – but how and why? Prostaglandins Leukot. Essent. Fatty Acids 78, 11–19 (2008).
   Google Scholar
• Das UN. Is depression a low‑grade systemic inflammatory condition? Am. J. Clin. Nutr. 85, 1665–1666 (2007).
   Google Scholar
• Dougan M, Dranoff G. Inciting inflammation: the RAGE about tumor promotion. J. Exp. Med. 205, 267–270 (2008).
   Google Scholar
• Visser M, Bouter LM, McQuillan GM et al. Elevated C‑reactive protein levels in overweight and obese adults. JAMA 282, 2131–2135 (1999). One of the first reports suggesting that inflammatory markers are elevated in obesity.
   Google Scholar
• Hotamisligil GS. The role of TNF‑alpha and TNF receptors in obesity and insulin resistance. J. Intern. Med. 245, 621–625 (1999).
   Google Scholar
• Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C‑reactive protein, interleukin‑6, and risk of developing Type 2 diabetes mellitus. JAMA 286, 327–334 (2001).
   Google Scholar
• Das UN. GLUT‑4, tumor necrosis factor, essential fatty acids and daf‑genes and their role in glucose homeostasis, insulin resistance, non‑insulin dependent diabetes mellitus and longevity. J. Assoc. Physicians India 47, 431–435 (1999).
   Google Scholar
• Fichtlscherer S, Rosenberger G, Walter DH et al. Elevated C‑reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 102, 1000–1006 (2000).
   Google Scholar
• Cleland SJ, Sattar N, Petrie JR et al. Endothelial dysfunction as a possible link between C‑reactive protein levels and cardiovascular disease. Clin. Sci. (Lond.) 98, 531–535 (2000).
   Google Scholar
• Das UN. Non‑alcoholic fatty liver disease as a pro‑resolution defective disorder. Nutrition 29, 345–349 (2013).
   Google Scholar
• Das UN. Lipoxins, resolvins, protectins, maresins, and nitrolipids: connecting lipids, inflammation, and cardiovascular disease risk. Curr. Cardio. Risk Rep. 4, 24–31 (2010).
   Google Scholar
• Das UN. Cross talk among leukocytes, platelets, and endothelial cells and its relevance to atherosclerosis and coronary heart disease. Current Nutr. Food Sci. 5, 75–93 (2009).
   Google Scholar
• Das UN. Is multiple sclerosis a proresolution deficiency disorder? Nutrition 28, 951–958 (2012).
   Google Scholar
• Popp J, Bacher M, Kölsch H et al. Macrophage migration inhibitory factor in mild cognitive impairment and Alzheimer’s disease. J. Psychiatr. Res. 43, 749–753 (2009).
   Google Scholar
• Patel NS, Paris D, Mathura V, Quadros AN, Crawford FC, Mullan MJ. Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer’s disease. J. Neuroinflammation 2, 9 (2005).
   Google Scholar
• Sutton ET, Thomas T, Bryant MW, Landon CS, Newton CA, Rhodin JA. Amyloid‑beta peptide induced inflammatory reaction is mediated by the cytokines tumor necrosis factor and interleukin‑1. J. Submicrosc. Cytol. Pathol. 31, 313–323 (1999).
   Google Scholar
• Wei H, Zou H, Sheikh AM et al. IL‑6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J. Neuroinflammation 8, 52 (2011).
   Google Scholar
• Das UN. A defect in the activities of D6 and D5 desaturases and pro‑resolution bioactive lipids in the pathobiology of non‑alcoholic fatty liver disease. World J. Diabetes 2, 176–188 (2011).
   Google Scholar
• Stephen FD, Kelleher RJ Jr, Langner M, Repasky EA. Dietary fatty acids alter the adhesion properties of lymphocytes to extracellular matrix proteins. Adv. Exp. Med. Biol. 400B, 775–788 (1997).
   Google Scholar
• Spector AA, Yorek MA. Membrane lipid composition and cellular function. J. Lipid Res. 26, 1015–1035 (1985).
   Google Scholar
• Das UN. Essential fatty acids: biochemistry, physiology, and pathology. Biotech. J. 1, 420–439 (2006).
   Google Scholar
• Das UN. Essential fatty acids – a review. Current Pharmaceut. Biotech. 7, 467–482 (2006).
   Google Scholar
• Das UN. Biological significance of essential fatty acids. J. Assoc. Physicians India 54, 309–319 (2006).
   Google Scholar
• Das UN, Mohan IK, Raju TR. Effect of corticosteroids and eicosapentaenoic acid/docosahexaenoic acid on pro‑oxidant and anti‑oxidant status and metabolism of essential fatty acids in patients with glomerular disorders. Prostaglandins Leukot. Essent. Fatty Acids 65, 197–203 (2001).
   Google Scholar
• Das UN. Long‑chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor‑β to prevent human essential hypertension. Eur. J. Clin. Nutr. 58, 195–203 (2004).
   Google Scholar
• Das UN. Can perinatal supplementation of long‑chain polyunsaturated fatty acids prevent diabetes mellitus? Eur. J. Clin. Nutr. 57, 218–226 (2003).
   Google Scholar
• Das UN. Molecular Basis of Health and Disease. Springer, NY, USA (2011). Comprehensive book in which the role of inflammation in several clinical conditions is discussed and the role of anti-inflammatory bioactive lipids in these diseases outlined.
   Google Scholar
• Baker PR, Lin Y, Schopfer FJ et al. Fatty acid transduction of nitric oxide signaling: multiple nitrated unsaturated fatty acid derivatives exist in human blood and urine and serve as endogenous peroxisome proliferator‑activated receptor ligands. J. Biol. Chem. 280, 42464–42475 (2005).
   Google Scholar
• Coles B, Bloodsworth A, Clark SR et al. Nitrolinoleate inhibits superoxide generation, degranulation, and integrin expression by human neutrophils. Circ. Res. 91, 375–381 (2002). Biological function of nitrolipids is discussed.
   Google Scholar
• Lima ES, Bonim MG, Augusto O, Barbeiro HV, Souza HP, Abdalla DS. Nitrated lipidsdecompose to nitric oxide and lipid radicals and cause vasorelaxation. Free Radic. Biol. Med. 39, 532–539 (2005).
   Google Scholar
• Wright MM, Schopfer FJ, Baker PRS et al. Fatty acid transduction of nitric oxide signaling: nitrolinoleic acid potently activates endothelial heme oxygenase 1 expression. Proc. Natl Acad. Sci. USA 103, 4299–4304 (2006).
   Google Scholar
• Claria J, Serhan CN. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell–leukocyte interactions. Proc. Natl Acad. Sci. USA 92, 9475–9479 (1995). The formation of anti-inflammatory lipoxins is discussed.
   Google Scholar
• Chiang N, Gronert K, Clish CB, O’Brien JA, Freeman MW, Serhan CN. Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirintriggered lipoxins in reperfusion. J. Clin. Invest. 104, 309–316 (1999).
   Google Scholar
• Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K. Novel functional sets of lipid‑derived mediators with anti‑inflammatory actions generated from omega‑3 fatty acids via cyclo‑oxygenase 2‑nonsteroidal antiinflammatory drugs and transcellular processing. J. Exp. Med. 192, 1197–1204 (2000). Formation and actions of resolvins is discussed.
   Google Scholar
• Serhan CN, Hong S, Gronert K et al. Resolvins: a family of bioactive products of omega‑3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 196, 1025–1037 (2002).
   Google Scholar
• Marcheselli VL, Hong S, Lukiw WJ et al. Novel docosanoids inhibit brain ischemia‑reperfusion‑mediated leukocyte infiltration and pro‑inflammatory gene expression. J. Biol. Chem. 278, 43807–43817 (2003).
   Google Scholar
• Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN. Novel docosatrienes and 17S‑resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti‑inflammation. J. Biol. Chem. 278, 14677–14687 (2003).
   Google Scholar
• Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG. Neuroprotectin D1: a docosahexaenoic acid‑derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc. Natl Acad. Sci. USA 101, 8491–8496 (2004). The cytoprotective action of neuroprotectin is outlined.
   Google Scholar
• Gronert K, Maheshwari N, Khan N, Hasan IR, Dunn M, Schwartzman ML. A role for the mouse 12/15‑lipoxygenase pathway in promoting epithelial wound healing and host defense. J. Biol. Chem. 280, 15267–15278 (2005).
   Google Scholar
• Serhan CN, Yang R, Martinod K et al. Maresins: novel macrophage mediators with potent anti‑inflammatory and proresolving actions. J. Exp. Med. 206, 15–23 (2009). Formation and actions of anti-inflammatory maresins is discussed.
   Google Scholar
• Serhan CN. Systems approach to inflammation resolution: identification of novel anti‑inflammatory and pro‑resolving mediators. J. Thromb. Haemost. 7(Suppl. 1), 44–48 (2009).
   Google Scholar
• Baker PR, Lin Y, Schopfer FJ et al. Fatty acid transduction of nitric oxide signaling: multiple nitrated unsaturated fatty acid derivatives exist in human blood and urine and serve as endogenous peroxisome proliferator‑activated receptor ligands. J. Biol. Chem. 280, 42464–42475 (2005). One of the first descriptions of the presence of nitrolipids in human blood and urine.
   Google Scholar
• Woodcock SR, Marwitz AJ, Bruno P, Branchaud BP. Synthesis of nitrolipids. All four possible diastereomers of nitrooleic acids: (E)‑ and (Z)‑, 9‑ and 10‑nitro‑octadec‑9‑enoic acids. Org. Lett. 8, 3931–3934 (2006).
   Google Scholar
• Zanoni G, Valli M, Bendjeddou L, Porta A, Bruno P, Vidari G. Improved synthesis of (E)‑12‑nitrooctadec‑12‑enoic acid, a potent PPARg activator. Development of a “bufferfree” enzymatic method for hydrolysis of methyl esters. J. Org. Chem. 75, 8311–8314 (2010).
   Google Scholar
• Dunny E, Evans P. Stereocontrolled synthesis of the PPAR‑gamma agonist 10‑nitrolinoleic acid. J. Org. Chem. 75, 5334–5336 (2010).
   Google Scholar
• Manini P, Camera E, Picardo M, Napolitano A, d’Ischia M. Biomimetic nitration of the linoleic acid metabolite 13‑hydroxyoctadecadienoic acid: isolation and spectral characterization of novel chainrearranged epoxy nitro derivatives. Chem. Phys. Lipids 151, 51–61 (2008).
   Google Scholar
• O’Donnell VB, Eiserich JP, Chumley PH et al. Nitration of unsaturated fatty acids by nitric oxide‑derived reactive nitrogen species peroxynitrite, nitrous acid, nitrogen dioxide, and nitronium ion. Chem. Res. Toxicol. 12, 83–92 (1999).
   Google Scholar
• O’Donnell VB, Eiserich JP, Bloodsworth A et al. Nitration of unsaturated fatty acids by nitric oxide‑derived reactive species. Methods Enzymol. 301, 454–470 (1999).
   Google Scholar
• Schopfer FJ, Baker PR, Giles G et al. Fatty acid transduction of nitric oxide signaling. Nitrolinoleic acid is a hydrophobically stabilized nitric oxide donor. J. Biol. Chem. 280, 19289–19297 (2005).
   Google Scholar
• Khoo NK, Freeman BA. Electrophilic nitrofatty acids: anti‑inflammatory mediators in the vascular compartment. Curr. Opin. Pharmacol. 10, 179–184 (2010).
   Google Scholar
• Heiss EH, Schachner D, Werner ER, Dirsch VM. Active NF‑E2‑related factor (Nrf2) contributes to keep endothelial NO synthase (eNOS) in the coupled state: role of BRCA1 species (ROS), eNOS, and heme oxygenase (HO‑1) levels. J. Biol. Chem. 284, 31579–31586 (2009).
   Google Scholar
• Das UN. Current and emerging strategies for the treatment and management of systemic lupus erythematosus based on molecular signatures of acute and chronic inflammation. J. Inflamm. Res. 3, 143–170 (2010).
   Google Scholar
• Kalyanaraman B. Nitrated lipids: a class of cell‑signaling molecules. Proc. Natl Acad. Sci. USA 101, 11527–11528 (2004).
   Google Scholar
• Baker PR, Schopfer FJ, Sweeney S, Freeman BA. Red cell membrane and plasma linoleic acid nitration products: synthesis, clinical identification, and quantitation. Proc. Natl Acad. Sci. USA 101, 11577–11582 (2004).
   Google Scholar
• Jiang H, Kruger N, Lahiri DR, Wang D, Vatèle JM, Balazy M. Nitrogen dioxide induces cis‑trans‑isomerization of arachidonic acid within cellular phospholipids. Detection of trans‑arachidonic acids in vivo. J. Biol. Chem. 274, 16235–16241 (1999).
   Google Scholar
• Krishna UM, Reddy MM, Xia J, Falck JR, Balazy M. Stereospecific synthesis of transarachidonic acids. Bioorg. Med. Chem. Lett. 11, 2415–2418 (2001).
   Google Scholar
• Roy U, Loreau O, Balazy M. Cytochrome P450/NADPH‑dependent formation of trans epoxides from trans‑arachidonic acids. Bioorg. Med. Chem. Lett. 14, 1019–1022 (2004).
   Google Scholar
• Roy U, Joshua R, Stark RL, Balazy M. Cytochrome P450/NADPH‑dependent biosynthesis of 5,6‑trans‑epoxyeicosatrienoic acid from 5,6‑trans‑arachidonic acid. Biochem. J. 390(Pt 3), 719–727 (2005).
   Google Scholar
• Zghibeh CM, Raj Gopal V, Poff CD, Falck JR, Balazy M. Determination of transarachidonic acid isomers in human blood plasma. Anal. Biochem. 332, 137–144 (2004). One of the early studies describing the presence of trans-arachidonic acid in human blood.
   Google Scholar
• Zeid NA, Muller HK. Tobacco smoke induced lung granulomas and tumors: association with pulmonary Langerhans cells. Pathology 27, 247–254 (1995).
   Google Scholar
• Roth MD, Arora A, Barsky SH, Kleerup EC, Simmons M, Tashkin DP. Airway inflammation in young marijuana and tobacco smokers. Am. J. Respir. Crit. Care Med. 157(3 Pt 1), 928–937 (1998).
   Google Scholar
• Liu ES, Ye YN, Shin VY et al. Cigarette smoke exposure increases ulcerative colitisassociated colonic adenoma formation in mice. Carcinogenesis 24, 1407–1413 (2003).
   Google Scholar
• Ye YN, Liu ES, Shin VY, Wu WK, Cho CH. Contributory role of 5‑lipoxygenase and its association with angiogenesis in the promotion of inflammation‑associated colonic tumorigenesis by cigarette smoking. Toxicology 203, 179–188 (2004).
   Google Scholar
• Ye YN, Wu WK, Shin VY, Bruce IC, Wong BC, Cho CH. Dual inhibition of 5‑LOX and COX‑2 suppresses colon cancer formation promoted by cigarette smoke. Carcinogenesis 26, 827–834 (2005).
   Google Scholar
• Orosz Z, Csiszar A, Labinskyy N et al. Cigarette smoke‑induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation. Am. J. Physiol. Heart Circ. Physiol. 292, H130–H139 (2007).
   Google Scholar
• Borovikova LV, Ivanova S, Zhang M et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462 (2000). One of the first reports describing the anti-inflammatory actions of acetylcholine.
   Google Scholar
• Das UN. Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus? Lipids Health Dis. 10, 19 (2011).
   Google Scholar
• Das UN. Vagal nerve stimulation in prevention and management of coronary heart disease. World J. Cardiol. 3, 105–110 (2011).
   Google Scholar
• Wang H, Yu M, Ochani M et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421, 384–388 (2003).
   Google Scholar
• Diehn M, Cho RW, Lobo NA et al. Association of BRCA1 species levels and radioresistance in cancer stem cells. Nature 458, 780–785 (2009).
   Google Scholar
• Singh VN, Singh M, August JT, Horecker BL. Alterations in glucose metabolism in chick‑embryo cells transformed by Rous sarcoma virus: intracellular levels of glycolytic intermediates. Proc. Natl Acad. Sci. USA 71, 4129–4132 (1974).
   Google Scholar
• Das UN. Ethyl pyruvate and sepsis. Adv. Sepsis 6, 10–15 (2007).
   Google Scholar
• Das UN. Is pyruvate an endogenous anti‑inflammatory molecule? Nutrition 22, 965–972 (2006).
   Google Scholar
• Aykin‑Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem. J. 418, 29–37 (2009).
   Google Scholar
• Lopez‑Lazaro M. A new view of carcinogenesis and an alternative approach to cancer therapy. Mol. Med. 16, 144–153 (2010).
   Google Scholar
• Lawrence T, Hagemann T, Balkwill F. Sex, cytokines, and cancer. Science 317, 51–52 (2007).
   Google Scholar
• Mantovani A. Inflaming metastasis. Nature 457, 36–37 (2009).
   Google Scholar
• Balkwill F. Tumor necrosis factor and cancer. Nat. Rev. 9, 361–371 (2009).
   Google Scholar
• Dougan M, Dranoff G. Inciting inflammation: the RAGE about tumor promotion. J. Exp. Med. 205, 267–270 (2008).
   Google Scholar
• Gebhardt C, Riehl A, Durchdewald M et al. RAGE signaling sustains inflammation and promotes tumor development. J. Exp. Med. 205, 275–285 (2008).
   Google Scholar
• Simmons PM, Salmon JA, Moncada S. The release of leukotriene B4 during experimental inflammation. Biochem. Pharmacol. 32, 1353–1359 (1983).
   Google Scholar
• Das UN. Interaction(s) between essential fatty acids, eicosanoids, cytokines, growth factors and free radicals: relevance to new therapeutic strategies in rheumatoid arthritis and other collagen vascular diseases. Prostaglandins Leukot. Essent. Fatty Acids 44, 201–210 (1991).
   Google Scholar
• Sala A, Zarini S, Bolla M. Leukotrienes: lipid bioeffectors of inflammatory reactions. Biochemistry (Mosc.) 63, 84–92 (1998).
   Google Scholar
• Ohuchi K, Watanabe M, Takahashi C et al. Analysis of tumor‑promoter‑induced inflammation in rats: participation of histamine and prostaglandin E2. Biochim. Biophys. Acta 925, 156–163 (1987).
   Google Scholar
• Qualtrough D, Kaidi A, Chell S, Jabbour HN, Williams AC, Paraskeva C. Prostaglandin F(2alpha) stimulates motility and invasion in colorectal tumor cells. Int. J. Cancer 121, 734–740 (2007).
   Google Scholar
• Chell SD, Witherden IR, Dobson RR et al. Increased EP4 receptor expression in colorectal cancer progression promotes cell growth and anchorage independence. Cancer Res. 66, 3106–3113 (2006).
   Google Scholar
• Pai R, Nakamura T, Moon WS, Tarnawski AS. Prostaglandins promote colon cancer cell invasion; signaling by cross‑talk between two distinct growth factor receptors. FASEB J. 17, 1640–1647 (2003).
   Google Scholar
• Han C, Michalopoulos GK, Wu T. Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells. J. Cell. Physiol. 207, 261–270 (2006).
   Google Scholar
• Han C, Wu T. Cyclooxygenase‑2‑derived prostaglandin E2 promotes human cholangiocarcinoma cell growth and invasion through EP1 receptor‑mediated activation of the epidermal growth factor receptor and Akt. J. Biol. Chem. 280, 24053–24063 (2005).
   Google Scholar
• Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN. Modulation of apoptosis and Bcl‑2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res. 58, 362–366 (1998).
   Google Scholar
• Sheng H, Shao J, Washington MK, DuBois RN. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J. Biol. Chem. 276, 18075–18081 (2001).
   Google Scholar
• Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a Gs‑axin‑beta‑catenin signaling axis. Science 310, 1504–1510 (2005).
   Google Scholar
• Shao J, Jung C, Liu C, Sheng H. Prostaglandin E2 Stimulates the betacatenin/T cell factor‑dependent transcription in colon cancer. J. Biol. Chem. 280, 26565–26572 (2005).
   Google Scholar
• Dajani OF, Meisdalen K, Guren TK et al. Prostaglandin E2 upregulates EGF‑stimulated signaling in mitogenic pathways involving Akt and ERK in hepatocytes. J. Cell. Physiol. 214, 371–380 (2008).
   Google Scholar
• Shao J, Sheng H. Prostaglandin E2 induces the expression of IL‑1alpha in colon cancer cells. J. Immunol. 178, 4097–4103 (2007).
   Google Scholar
• Csiki I, Morrow JD, Sandler A et al. Targeting cyclooxygenase‑2 in recurrent nonsmall cell lung cancer: a Phase II trial of celecoxib and docetaxel. Clin. Cancer Res. 11, 6634–6640 (2005).
   Google Scholar
• Neale ML, Fiera RA, Matthews N. Involvement of phospholipase A2 activation in tumour cell killing by tumour necrosis factor. Immunology 64, 81–85 (1988).
   Google Scholar
• Reid T, Ramesha CS, Ringold GM. Resistance to killing by tumor necrosis factor in an adipocyte cell line caused by a defect in arachidonic acid biosynthesis. J. Biol. Chem. 266, 16580–16586 (1991).
   Google Scholar
• Vadas P, Pruzanski W, Stefanski E et al. Extracellular phospholipase A2 secretion is a common effector pathway of interleukin‑1 and tumour necrosis factor action. Immunol. Lett. 28, 187–193 (1991).
   Google Scholar
• Suffys P, Beyaert R, De Valck D, Vanhaesebroeck B, Van Roy F, Fiers W. Tumour‑necrosis‑factor‑mediated cytotoxicity is correlated with phospholipase‑A2 activity, but not with arachidonic acid release per se. Eur. J. Biochem. 195, 465–475 (1991).
   Google Scholar
• Hayakawa M, Ishida N, Takeuchi K et al. Arachidonic acid‑selective cytosolic phospholipase A2 is crucial in the cytotoxic action of tumor necrosis factor. J. Biol. Chem. 268, 11290–11295 (1993). The essentiality of arachidonic acid for the tumoricidal action of TNF is presented.
   Google Scholar
• Levrat C, Louisot P. Increase of mitochondrial PLA2‑released fatty acids is an early event in tumor necrosis factor alphatreated WEHI‑164 cells. Biochem. Biophys. Res. Commun. 221, 531–538 (1996).
   Google Scholar
• Wu YL, Jiang XR, Newland AC, Kelsey SM. Failure to activate cytosolic phospholipase A2 causes TNF resistance in human leukemic cells. J. Immunol. 160, 5929–5935 (1998).
   Google Scholar
• El Mahdani NE, Ameyar M, Cai Z, Colard O, Masliah J, Chouaib S. Resistance to TNFinduced cytotoxicity correlates with an abnormal cleavage of cytosolic phospholipase A2. J. Immunol. 165, 6756–6761 (2000).
   Google Scholar
• Wolf LA, Laster SM. Characterization of arachidonic acid‑induced apoptosis. Cell Biochem. Biophys. 30, 353–368 (1999).
   Google Scholar
• Brekke OL, Espevik T, Bardal T, Bjerve KS. Effects of n‑3 and n‑6 fatty acids on tumor necrosis factor cytotoxicity in WEHI fibrosarcoma cells. Lipids 27, 161–168 (1992).
   Google Scholar
• Brekke OL, Sagen E, Bjerve KS. Specificity of endogenous fatty acid release during tumor necrosis factor‑induced apoptosis in WEHI 164 fibrosarcoma cells. J. Lipid Res. 40, 2223–2233 (1999).
   Google Scholar
• Das UN. Cis‑unsaturated fatty acids as potential anti‑mutagenic, tumoricidal and anti‑metastatic agents. Asia Pacific J. Pharmacol. 7, 305–327 (1992).
   Google Scholar
• Galeotti T, Borrello S, Masoti L. Oxy radical sources, scavenger systems and membrane damage in cancer cells. In: Oxygen Radicals: Systemic Events and Disease Processes. Das DK, Essman WB (Eds). Karger, Basel, Switzerland, 129–148 (1990).
   Google Scholar
• Dianzani MU, Rossi MA. Lipid peroxidation in tumors. In: Recent Trends in Chemical Carcinogenesis (Volume 1). Pani P, Feo F, Columbano A, Cagliari ES (Eds). ESA, Cagliari, Italy, 243–257 (1981). One of the early reports describing the alterations in the lipid peroxidation process in tumor cells.
   Google Scholar
• Bartoli GM, Galeotti T. Growth‑related lipid peroxidation in tumor microsomal membranes and mitochondria. Biochim. Biophys. Acta 574, 537–541 (1979).
   Google Scholar
• Hostetler KY, Zenner BD, Morris HP. Phospholipid content of mitochondrial and microsomal membranes from Morris hepatomas of varying growth rates. Cancer Res. 39, 2978–2983 (1979).
   Google Scholar
• Hartz JW, Morton RE, Waite MM, Morris HP. Correlation of fatty acyl composition of mitochondrial and microsomal phospholipid with growth rate of rat hepatomas. Lab. Invest. 46, 73–78 (1982).
   Google Scholar
• Cheeseman KH, Emery S, Maddix SP, Slater TF, Burton GW, Ingold K. Studies on lipid peroxidation in normal and tumour tissue. The Yoshida rat liver tumour. Biochem. J. 250, 247–252 (1988).
   Google Scholar
• Cheeseman KH, Burton GW, Ingold KU, Slater TF. Lipid peroxidation and lipid antioxidants in normal and tumor cells. Toxicol. Pathol. 12, 235–239 (1984).
   Google Scholar
• Borrello S, Minotti G, Galeotti T. Factors influencing O2 and t‑Bu OOH‑dependent lipid peroxidation of tumor microsomes. In: Superoxide and Superoxide Dismutase in Chemistry, Biology and Medicine. Rotilio G (Ed.). Elsevier, Amsterdam, The Netherlands, 323–324 (1988).
   Google Scholar
• Das UN, Begin ME, Ells G, Huang YS, Horrobin DF. Polyunsaturated fatty acids augment free radical generation in tumor cells in vitro. Biochem. Biophys. Res. Commun. 145, 15–24 (1987). One of the early reports showing that polyunsaturated fatty acids kill tumor cells by augmenting the lipid peroxidation process.
   Google Scholar
• Das UN, Huang YS, Begin ME, Ells G, Horrobin DF. Uptake and distribution of cis‑unsaturated fatty acids and their effect on free radical generation in normal and tumor cells in vitro. Free Radic. Biol. Med. 3, 9–14 (1987).
   Google Scholar
• Das UN. Selective enhancement of free radicals in tumor cells as a strategy to kill tumor cells both in vitro and in vivo. In: Biological Oxidation Systems (Volume 2). Reddy CC, Hamilton GA, Madyastha KM (Eds). Academic Press, NY, USA, 607–624 (1990).
   Google Scholar
• Bendetti A. Loss of lipid peroxidation as an histochemical marker for preneoplastic hepatocellular foci of rats. Cancer Res. 44, 5712–5717 (1984).
   Google Scholar
• Dunbar LM, Bailey JM. Enzyme deletions and essential fatty acid metabolism in cultured cells. J. Biol. Chem. 250, 1152–1153 (1975). An early report showing that tumor cells are deficient in desaturase enzymes.
   Google Scholar
• Morton RE, Hartz JW, Reitz RC, Waite BM, Morris H. The acyl‑CoA desaturases of microsomes from rat liver and the Morris 7777 hepatoma. Biochim. Biophys. Acta 573, 321–331 (1979).
   Google Scholar
• Nassar BA, Das UN, Huang YS, Ells G, Horrobin DF. The effect of chemical hepato carcinogenesis on liver phospholipid composition in rats fed n‑6 and n‑3 fatty acid‑supplemented diets. Proc. Soc. Exp. Biol. Med. 199, 365–368 (1992).
   Google Scholar
• Tisdale MJ, Mahmoud MD. Activities of free radical metabolizing enzymes in tumours. Br. J. Cancer 47, 809–812 (1983).
   Google Scholar
• Bize IB, Oberley LW, Morris HP. Superoxide dismutase and superoxide radical in Morris hepatomas. Cancer Res. 40, 3686–3693 (1980).
   Google Scholar
• Halliwell B, Gutteridge JM. Free Radicals in Biology and Medicine (3rd Edition). Oxford University Press, Oxford, UK (1999).
   Google Scholar
• Morisaki N, Lindsey JA, Stitts JM, Zhang H, Cornwell DG. Fatty acid metabolism and cell proliferation. V. Evaluation of pathways for the generation of lipid peroxides. Lipids 19, 381–394 (1984).
   Google Scholar
• Morisaki N, Sprecher H, Milo GE, Cornwell DG. Fatty acid specificity in the inhibition of cell proliferation and its relationship to lipid peroxidation and prostaglandin biosynthesis. Lipids 17, 893–899 (1982).
   Google Scholar
• Liepkalns VA, Icard‑Liepkalns C, Cornwell DG. Regulation of cell division in a human glioma cell clone by arachidonic acid and alpha‑tocopherol quinone. Cancer Lett. 15, 173–178 (1982).
   Google Scholar
• Tolnai S, Morgan JF. Studies on the in vitro anti‑tumor activity of fatty acids. V. Unsaturated fatty acids. Can. J. Biochem. Physiol. 40, 869–875 (1962).
   Google Scholar
• Rossi MA, Cecchini G. Lipid peroxidation in hepatomas of different degrees of deviation. Cell Biochem. Function 1, 49–54 (1983).
   Google Scholar
• Burlakova EB, Palmina NP. On the possible role of free radical mechanism on the regulation of cell replication. Biofizika 12, 82–88 (1967).
   Google Scholar
• Gonzalez M, Schemmel R, Dugan L, Gray J, Welsch C. Dietary fish oil inhibits human breast carcinoma growth: a function of increased lipid peroxidation. Lipids 28, 827–832 (1993).
   Google Scholar
• Carini C, Hudspith BN, Brostoff J. Effect of prostaglandins and cyclic nucleotides on growth and immunoglobulin secretion of two IgE myeloma cell lines. Br. J. Cancer 43, 257–260 (1981).
   Google Scholar
• Nakamura M, Koshihara Y, Fujino Y, Mochizuki M, Minoda K, Masuda K. In vitro effects of prostaglandins on human retinoblastoma cell line, Y‑79 cells. Jpn J. Ophthalmol. 31, 598–607 (1987).
   Google Scholar
• Das UN. Tumoricidal and anti‑angiogenic actions of gamma‑linolenic acid and its derivatives. Current Pharmaceut. Biotech. 7, 457–466 (2006).
   Google Scholar
• Cao Y, Pearman AT, Zimmerman GA, McIntyre TM, Prescott SM. Intracellular unesterified arachidonic acid signals apoptosis. Proc. Natl Acad. Sci. USA 97, 11280–11285 (2000).
   Google Scholar
• Brekke OL, Sagen E, Bjerve KS. Specificity of endogenous fatty acid release during tumor necrosis factor‑induced apoptosis in WEHI 164 fibrosarcoma cells. J. Lipid Res. 40, 2223–2233 (1999).
   Google Scholar
• Ramesh G, Das UN. Effect of free fatty acids on two stage skin carcinogenesis in mice. Cancer Lett. 100, 199–209 (1996).
   Google Scholar
• Calviello G, Palozza O, Piccioni E et al. Supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: effects on proliferation and apoptosis. Int. J. Cancer 75, 699–705 (1998).
   Google Scholar
• El‑Ela SH, Prasse KW, Carroll R. Effects of dietary primrose oil on mammary tumorigenesis induced by 7, 12‑dimethyl bez(a) anthracene. Lipids 22, 1041–1044 (1987).
   Google Scholar
• El‑Ela SH, Prasse KW, Carroll R, Wade AE, Dharwadkar S, Bunce OR. Eicosanoids synthesis in 7, 12‑dimethylbenz(a) anthracene‑induced mammary carcionomas in Sprague‑Dawley rats fed primrose oil, menhaden oil or corn oil diet. Lipids 23, 948–954 (1988).
   Google Scholar
• Cameron E, Bland J, Marcuson R. Divergent effects of omega‑6 and omega‑3 fatty acids on mammary tumor development in C3H/Heston mice treated with DMBA. Nutrition Res. 9, 383–393 (1989).
   Google Scholar
• Ramesh G, Das UN, Koratkar R, Padma M, Sagar PS. Effect of essential fatty acids on tumor cells. Nutrition 8, 343–347 (1992).
   Google Scholar
• Menendez JA, del Mar Barbacid M et al. Effects of gamma‑linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. Eur. J. Cancer 37, 402–413 (2001).
   Google Scholar
• Kenny FS, Gee JM, Nicholson RI et al. Effect of dietary GLA+/‑ tamoxifen on growth and ER in a human breast cancer xenograft model. Eur. J. Cancer 34(Suppl. 5), S20 (1998).
   Google Scholar
• Kenny FS, Pinder S, Ellis IO, Bryce RP, Hartley J, Robertson JF. Gamma linolenic acid with tamoxifen as primary therapy in breast cancer. Eur. J. Cancer 34(Suppl. 5), S18–S19 (1998).
   Google Scholar
• Iwamoto S, Senzaki H, Kiyozuka Y et al. Effects of fatty acids on liver metastasis of ACL‑15 rat colon cancer cells. Nutr. Cancer 31, 143–150 (1998).
   Google Scholar
• Sakaguchi M, Rowley S, Kane N et al. Reduced tumour growth of the human colonic cancer cell lines COLO‑320 and HT‑29 in vivo by dietary n‑3 lipids. Br. J. Cancer 62, 742–747 (1990).
   Google Scholar
• Rose DP, Connolly JM, Rayburn J, Coleman M. Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice. J. Natl Cancer Inst. 87, 587–592 (1995).
   Google Scholar
• Boudreau MD, Sohn KH, Rhee SH, Lee SW, Hunt JD, Hwang DH. Suppression of tumor cell growth both in nude mice and in culture by n‑3 polyunsaturated fatty acids: mediation through cyclooxygenase‑independent pathways. Cancer Res. 61, 1386–1391 (2001).
   Google Scholar
• Kato T, Kolenic N, Pardini RS. Docosahexaenoic acid (DHA), a primary tumor suppressive omega‑3 fatty acid, inhibits growth of colorectal cancer independent of p53 mutational status. Nutr. Cancer 58, 178–187 (2007).
   Google Scholar
• Ding WQ, Vaught JL, Yamauchi H, Lind SE. Differential sensitivity of cancer cells to docosahexaenoic acid‑induced cytotoxicity: the potential importance of down‑regulation of superoxide dismutase 1 expression. Mol. Cancer Ther. 3, 1109–1117 (2004).
   Google Scholar
• Sravan Kumar G, Das UN. Free radical dependent suppression of mouse myeloma cells by alpha‑linolenic and eicosapentaenoic acids in vitro. Cancer Lett. 92, 27–38 (1995).
   Google Scholar
• Das UN, Madhavi N, Kumar SG, Padma M, Sangeetha P. Can tumor cell drug resistance be reversed by essential fatty acids and their metabolites? Prostaglandins Leukot. Essent. Fatty Acids 58, 39–54 (1998).
   Google Scholar
• Ding WQ, Lind SE. Phospholipid hydroperoxide glutathione peroxidase plays a role in protecting cancer cells from docosahexaenoic acid‑induced cytotoxicity. Mol. Cancer Ther. 6, 1467–1474 (2007).
   Google Scholar
• Miyake J, Benadiba M, Colquhoun A. 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. Lipids Health Dis. 8, 8 (2009). This study showed that g-linolenic acid (GLA) inhibits tumor growth by acting at the gene level.
   Google Scholar
• Faragó N, Fehér LZ, Kitajka K, Das UN, Puskás LG. MicroRNA profile of polyunsaturated fatty acid treated glioma cells reveal apoptosis‑specific expression changes. Lipids Health Dis. 10, 173 (2011).
   Google Scholar
• Monjazeb AM, High KP, Connoy A, Hart LS, Koumenis C, Chilton FH. Arachidonic acid‑induced gene expression in colon cancer cells. Carcinogenesis 27, 1950–1960 (2006).
   Google Scholar
• Kachhap SK, Dange P, Nath Ghosh S. Effect of omega‑6 polyunsaturated fatty acid (linoleic acid) on BRCA1 gene expression in MCF‑7 cell line. Cancer Lett. 154, 115–120 (2000).
   Google Scholar
• Kachhap SK, Dange PP, Santani RH, Sawant SS, Ghosh SN. Effect of omega‑3 fatty acid (docosahexanoic acid) on BRCA1 gene expression and growth in MCF‑7 cell line. Cancer. Biother. Radiopharm. 16, 257–263 (2001).
   Google Scholar
• Menendez JA, Ropero S, Mehmi I, Atlas E, Colomer R, Lupu R. Overexpression and hyperactivity of breast cancer‑associated fatty acid synthase (oncogenic antigen‑519) is insensitive to normal arachidonic fatty acidinduced suppression in lipogenic tissues but it is selectively inhibited by tumoricidal alphalinolenic and gamma‑linolenic fatty acids: a novel mechanism by which dietary fat can alter mammary tumorigenesis. Int. J. Oncol. 24, 1369–1383 (2004).
   Google Scholar
• Menendez JA, Colomer R, Lupu R. Inhibition of fatty acid synthase‑dependent neoplastic lipogenesis as the mechanism of gammalinolenic acid‑induced toxicity to tumor cells: an extension to Nwankwo’s hypothesis. Med. Hypotheses 64, 337–341 (2005).
   Google Scholar
• Menendez JA, Mehmi I, Atlas E, Colomer R, Lupu R. Novel signaling molecules implicated in tumor‑associated fatty acid synthasedependent breast cancer cell proliferation and survival: role of exogenous dietary fatty acids, p53‑p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF‑kappaB. Int. J. Oncol. 24, 591–608 (2004).
   Google Scholar
• Thupari JN, Pinn ML, Kuhajda FP. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl‑CoA‑induced inhibition of fatty acid oxidation and cytotoxicity. Biochem. Biophys. Res. Commun. 285, 217–223 (2001).
   Google Scholar
• Pizer ES, Thupari J, Han WF et al. Malonyl‑coenzyme‑A is a potential mediator of cytotoxicity induced by fatty‑acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res. 60, 213–218 (2000).
   Google Scholar
• Rose DP, Hatala MA, Connolly JM, Rayburn J. Effect of diets containing different levels of linoleic acid on human breast cancer growth and lung metastasis in nude mice. Cancer Res. 53, 4686–4690 (1993).
   Google Scholar
• Rose DP, Connolly JM, Liu XH. Dietary fatty acids and human breast cancer cell growth, invasion, and metastasis. Adv. Exp. Med. Biol. 364, 83–91 (1994).
   Google Scholar
• Rose DP, Connolly JM, Liu XH. Effects of linoleic acid on the growth and metastasis of two human breast cancer cell lines in nude mice and the invasive capacity of these cell lines in vitro. Cancer Res. 54, 6557–6562 (1994).
   Google Scholar
• Gleissman H, Yang R, Martinod K et al. Docosahexaenoic acid metabolome in neural tumors: identification of cytotoxic intermediates. FASEB J. 24, 906–915 (2010).
   Google Scholar
• Das UN. Essential fatty acids enhance free radical generation and lipid peroxidation to induce apoptosis of tumor cells. Clin. Lipidol. 6, 463–489 (2011).
   Google Scholar
• Devi GR, Das UN, Rao KP, Rao MS. Prostaglandins and mutagenesis: prevention and/or reversibility of genetic damage induced by benzo (a) pyrene in the bone marrow cells of mice by prostaglandins El. Prostaglandins Leukot. Med. 15, 287–292 (1984).
   Google Scholar
• Devi GR, Das UN, Rao KP, Rao MS. Prostaglandins and mutagenesis: modification of phenytoin‑induced genetic damage by prostaglandins in lymphocyte cultures. Prostaglandins Leukot. Med. 15, 109–113 (1984).
   Google Scholar
• Das UN, Devi GR, Rao KP, Rao MS. Prostaglandins and their precursors can modify genetic damage‑induced by gammaradiation and benzo(a)pyrene. Prostaglandins 29, 911–920 (1985). One of the first reports showing that certain polyunsaturated fatty acids and their products can inhibit radiation and chemically induced genetic damage in vivo.
   Google Scholar
• Das UN, Devi GR, Rao KP, Rao MS. Prostaglandins can modify gamma‑radiation and chemical induced cytotoxicity and genetic damage in vitro and in vivo. Prostaglandins 38, 689–716 (1989).
   Google Scholar
• Koratkar R, Das UN, Sagar PS et al. Prostacyclin is a potent anti‑mutagen. Prostaglandins Leukot. Essent. Fatty Acids 48, 175–184 (1993).
   Google Scholar
• Ponnala S, Rao KP, Chaudhury JR et al. Effect of polyunsaturated fatty acids on diphenyl hydantoin‑induced genetic damage in vitro and in vivo. Prostaglandins Leukot. Essent. Fatty Acids 80, 43–50 (2009). Documented that oral supplementation of GLA can reduce the amount of DNA damage in humans.
   Google Scholar
• Das UN, Rao KP. Effect of gamma‑linolenic acid and prostaglandins E1 on gamma‑ radiation and chemical‑induced genetic damage to the bone marrow cells of mice. Prostaglandins Leukot. Essent. Fatty Acids 74, 165–173 (2006).
   Google Scholar
• Kim SJ. Lipoxins formation by rat basophilic leukemia (RBL‑1) cells. Res. Commun. Chem. Pathol. Pharmacol. 68, 159–174 (1990).
   Google Scholar
• Ng CF, Lam BK, Pritchard KA Jr, Stemerman MB, Hejny P, Wong PY. Formation of lipoxins by rat basophilic leukemia cells. Adv. Prostaglandin Thromboxane Leukot. Res. 19, 128–131 (1989). One of the early reports showing that tumor cells can form lipoxins.
   Google Scholar
• Stenke L, Näsman‑Glaser B, Edenius C, Samuelsson J, Palmblad J, Lindgren JA. Lipoxygenase products in myeloproliferative disorders: increased leukotriene C4 and decreased lipoxin formation in chronic myeloid leukemia. Adv. Prostaglandin Thrombox. Leukot. Res. 21B, 883–836 (1991).
   Google Scholar
• Chen Y, Hao H, He S et al. Lipoxin A4 and its analogue suppress the tumor growth of transplanted H22 in mice: the role of antiangiogenesis. Mol. Cancer Ther. 9, 2164–2174 (2010). Demonstrates that lipoxins inhibit tumor growth.
   Google Scholar
• Hao H, Liu M, Wu P et al. Lipoxin A4 and its analog suppress hepatocellular carcinoma via remodeling tumor microenvironment. Cancer Lett. 309, 85–94 (2011).
   Google Scholar
• Zhang B, Jia H, Liu J et al. Depletion of regulatory T cells facilitates growth of established tumors: a mechanism involving the regulation of myeloid‑derived suppressor cells by lipoxin A4. J. Immunol. 185, 7199–7206 (2010). Demonstrates that lipoxins may have both tumor-inhibiting and -promoting actions, depending on its action on Tregs.
   Google Scholar
• Cezar‑de‑Mello PF, Nascimento‑Silva V, Villela CG, Fierro IM. Aspirin‑triggered Lipoxin A4 inhibition of VEGF‑induced endothelial cell migration involves actin polymerization and focal adhesion assembly. Oncogene 25, 122–129 (2006).
   Google Scholar
• Cezar‑de‑Mello PF, Vieira AM, Nascimento‑Silva V, Villela CG, Barja‑Fidalgo C, Fierro IM. ATL‑1, an analogue of aspirin‑triggered lipoxin A4, is a potent inhibitor of several steps in angiogenesis induced by vascular endothelial growth factor. Br. J. Pharmacol. 153, 956–965 (2008).
   Google Scholar
• Baker N, O’Meara SJ, Scannell M, Maderna P, Godson C. Lipoxin A4: anti‑inflammatory and anti‑angiogenic impact on endothelial cells. J. Immunol. 182, 3819–3826 (2009).
   Google Scholar
• Jin Y, Arita M, Zhang Q et al. Antiangiogenesis effect of the novel anti‑inflammatory and pro‑resolving lipid mediators. Invest. Ophthalmol. Vis. Sci. 50, 4743–4752 (2009).
   Google Scholar
• Liu S, Wu P, Ye D et al. Effects of lipoxin A(4) on CoCl(2)‑induced angiogenesis and its possible mechanisms in human umbilical vein endothelial cells. Pharmacology 84, 17–23 (2009).
   Google Scholar
• Leedom AJ, Sullivan AB, Dong B, Lau D, Gronert K. Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury. Am. J. Pathol. 176, 74–84 (2010).
   Google Scholar
• Chen Y, Hao H, He S et al. Lipoxin A4 and its analogue suppress the tumor growth of transplanted H22 in mice: the role of antiangiogenesis. Mol. Cancer Ther. 9, 2164–2174 (2010).
   Google Scholar
• Hao H, Liu M, Wu P et al. Lipoxin A4 and its analog suppress hepatocellular carcinoma via remodeling tumor microenvironment. Cancer Lett. 309, 85–94 (2011).
   Google Scholar
• Das UN. Essential fatty acids and their metabolites as modulators of stem cell biology with reference to inflammation, cancer and metastasis. Cancer Metastasis Rev. 30, 311–324 (2011).
   Google Scholar
• Das UN. Radiation resistance, invasiveness and metastasis are inflammatory events that could be suppressed by lipoxin A(4). Prostaglandins Leukot. Essent. Fatty Acids 86, 3–11 (2012).
   Google Scholar
• Madhavi N, Das UN. Effect of polyunsaturated fatty acids on drug‑sensitive and resistant tumor cells in vitro. Lipids Health Dis. 10, 159 (2011).
   Google Scholar
• Das UN. Gamma‑linolenic acid therapy of human glioma – a review of in vitro, in vivo, and clinical studies. Med. Sci. Monit. 13, RA119–RA131 (2007).
   Google Scholar
• Das UN. Tumoricidal and anti‑angiogenic actions of gamma‑linolenic acid and its derivatives. Curr. Pharm. Biotechnol. 7, 457–466 (2006).
   Google Scholar
• Das UN, Prasad VV, Reddy DR. Local application of gamma‑linolenic acid in the treatment of human gliomas. Cancer Lett. 94, 147–155 (1995). Clinical study that showed that intratumoral injection of GLA regresses glioma in humans.
   Google Scholar
• Das UN. Tumoricidal action of cisunsaturated fatty acids and their relationship to free radicals and lipid peroxidation. Cancer Lett. 56, 235–243 (1991).
   Google Scholar
• Russell R, Gori I, Pellegrini C, Kumar R, Achtari C, Canny GO. Lipoxin A4 is a novel estrogen receptor modulator. FASEB J. 25, 4326–4337 (2011).
   Google Scholar
• Macdonald LJ, Boddy SC, Denison FC, Sales KJ, Jabbour HN. A role for lipoxin A4 as an antiinflammatory mediator in the human endometrium. Reproduction 142, 345–352 (2011).
   Google Scholar