Multiple beneficial health effects of natural alkylglycerols from shark liver oil

Anne-Laure Deniau, Paul Mosset, Frédérique Pédrono, Romain Mitre, Damien Le Bot, Alain B Legrand, Anne-Laure Deniau, Paul Mosset, Frédérique Pédrono, Romain Mitre, Damien Le Bot, Alain B Legrand

Abstract

Alkylglycerols (alkyl-Gro) are ether lipids abundant in the liver of some elasmobranch fish species such as ratfishes and some sharks. Shark liver oil from Centrophorus squamosus (SLO), or alkyl-Gro mix from this source, have several in vivo biological activities including stimulation of hematopoiesis and immunological defences, sperm quality improvement, or anti-tumor and anti-metastasis activities. Several mechanisms are suggested for these multiple activities, resulting from incorporation of alkyl-Gro into membrane phospholipids, and lipid signaling interactions. Natural alkyl-Gro mix from SLO contains several alkyl-Gro, varying by chain length and unsaturation. Six prominent constituents of natural alkyl-Gro mix, namely 12:0, 14:0, 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro, were synthesized and tested for anti-tumor and anti-metastatic activities on a model of grafted tumor in mice (3LL cells). 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl- Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect. Multiple compounds and mechanisms are probably involved in the multiple activities of natural alkyl-Gro.

Keywords: alkylglycerols; anti-tumor activities; ether lipids; immunostimulation; shark liver oil.

Figures

Figure 1
Figure 1
1-O-alkyl-sn-glycerols obtained by chemical synthesis.

References

    1. Hallgren B, Larsson SO. The glyceryl ethers in man and cow. J. Lipid Res. 1962;3:39–43.
    1. Bordier CG, Sellier N, Foucault AP, Le Goffic F. Purification and characterization of deep sea shark Centrophorus squamosus liver oil 1-O-alkylglycerol ether lipids. Lipids. 1996;31:521–528.
    1. Linman JW, Long MJ, Korst DR, Bethell FH. Studies on the stimulation of hemopoiesis by batyl alcohol. J. Lab. Clin. Med. 1959;54:335–343.
    1. Brohult A, Brohult J, Brohult S, Joelsson I. Effect of alkoxyglycerols on the frequency of injuries following radiation therapy for carcinoma of the uterine cervix. Acta Obst. Gynecol. Scand. 1977;56:441–448.
    1. Brohult A, Brohult J, Brohult S. Regression of tumour growth after administration of alkoxyglycerols. Acta Obstet. Gynecol. Scand. 1978;57:79–83.
    1. Ngwenya BZ, Foster DM. Enhancement of antibody production by lysophosphatidylcholine and alkylglycerol. Proc. Soc. Exp. Biol. Med. 1991;196:69–75.
    1. Brohult A, Brohult J, Brohult S. Effect of irradiation and alkoxyglycerol treatment on the formation of antibodies after salmonella vaccination. Experientia. 1972;28:954–955.
    1. Debouzy J-C, Crouzier D, Lefebvre B, Dabouis V. Study of alkylglycerol containing shark liver oil: a physic chemical support for biological effects. Drug Target Insights. 2008;3:125–135.
    1. Hichami A, Duroudier V, Leblais V, Vernhet L, Le Goffic F, Ninio E, Legrand A. Modulation of platelet-activating-factor production by incorporation of naturally occurring 1-O-alkylglycerols in phospholipids of human leukemic monocyte-like cells THP-1. Eur. J. Biochem. 1997;250:242–248.
    1. Marigny K, Pédrono F, Martin-Chouly C, Youmine H, Saïag B, Legrand AB. Modulation of endothelial permeability by 1-O-alkylglycerols. Acta Physiol. Scand. 2002;176:263–268.
    1. Pédrono F, Cheminade C, Legrand AB. Natural 1-O-alkylglycerols reduce platelet-activating factor-induced release of [3H]-serotonin in rabbit platelets. Prostag. Leukot. Ess. Fatty Acids. 2004;71:19–23.
    1. Heymans F, Da Silva C, Marrec N, Godfroid J-J, Castagna M. Alkyl analogs of diacylglycerols as activators of protein kinase C. FEBS Lett. 1987;218:35–40.
    1. Kamido H, Eguchi H, Ikeda H, Imaizumi T, Yamana K, Hartvigsen K, Ravandi A, Kuksis A. Core aldehydes of alkyl glycerophosphocholines in atheroma induce platelet aggregation and inhibit endothelium-dependent arterial relaxation. J. Lipid Res. 2002;43:158–166.
    1. Hartvigsen K, Ravandi A, Harkewicz R, Kamido H, Bukhave K, Holmer G, Kuksis A. A-O- alkyl-2-(ω-oxo)acyl-sn-glycerols from shark liver oil and human milk fat are potential precursors of PAF mimics and GHB. Lipids. 2006;41:679–693.
    1. Kraus CS, Gervasi G, Fori G, Baldi E. Effect of platelet-activating factor on motility and acrosome reaction on human spermatozoa. Hum. Reprod. 1994;9:471–476.
    1. Fukuda A, Roudebush WE, Thatcher SS. Platelet-activating factor enhances the acrosome reaction, fertilization in vitro by subzonal sperm injection and resulting embryonic development in the rabbit. Hum. Reprod. 1994;9:94–99.
    1. Cheminade C, Gautier V, Hichami A, Allaume P, Le Lannou D, Legrand AB. 1-O-alkylglycerols improve boar sperm motility and fertility. Biol. Reprod. 2002;66:421–428.
    1. Mitre R, Cheminade C, Allaume P, Legrand P, Legrand AB. Oral intake of shark liver oil modifies lipid composition and improves motility and velocity of boar sperm. Theriogenology. 2004;62:1557–1566.
    1. Mitre R, Etienne M, Martinais S, Salmon H, Allaume P, Legrand P, Legrand AB. Humoral defence improvement and haematopoiesis stimulation in sows and offspring by oral supply of shark liver oil to mothers during gestation and lactation. Br. J. Nutr. 2005;94:753–762.
    1. Lewkowicz P, Banasik M, Glowacka E, Lewkowicz N, Tchorzewski H. Effect of high doses of shark liver oil supplementation on T cell polarization and peripheral blood polymorphonuclear cell function. Pol. Merk. Lek. 2005;18:686–692.
    1. Pedrono F, Martin B, Leduc C, Le Lan J, Saïag B, Legrand P, Moulinoux JP, Legrand AB. Natural alkylglycerols restrain growth and metastasis of grafted tumour in mice. Nutr. Cancer. 2004;48:64–69.
    1. Skopinska-Rózewska E, Krotkiewski M, Sommer E, Rogala E, Filewska M, Bialas-Chromiec B, Pastewka K, Skurzak H. Inhibitory effect of shark liver oil on cutaneous angiogenesis induced in Balb/c mice by syngeneic sarcoma L-1, human urinary bladder and human kidney tumour cells. Oncol. Rep. 1999;6:1341–1343.
    1. Presta M, Dell’Era P, Mitola S, Moroni E, Ronca R, Rusnati M. Fibroblast growth factor/Fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 2005;16:159–178.
    1. Pédrono F, Saïag B, Moulinoux J-P, Legrand AB. 1-O-alkylglycerols reduce the stimulating effects of bFGF on endothelial cell proliferation in vitro. Cancer Lett. 2007;251:317–322.
    1. Deniau A-L, Mosset P, Le Bot D, Legrand AB. Which alkylglycerols from shark liver oil have anti-tumour activities? Biochimie. 2010 doi: 10.1016/j.biochi.2009.12.010.
    1. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Meth. 1983;65:55–63.
    1. Erdlenbruch B, Jendrossek V, Eibl H, Lakomek M. Transient and controllable opening of the blood-brain barrier to cytostatic and antibiotic agents by alkylglycerols in rats. Exp. Brain Res. 2000;135:417–422.
    1. Erdlenbruch B, Jendrossek V, Kugler W, Eibl H, Lakomek M. Increased delivery of erucylphosphocholine to C6 gliomas by chemical opening of the blood-brain barrier using intracarotid alkylglycerols in rats. Cancer Chemother. Pharmacol. 2002;50:299–304.
    1. Madhusudhan B, Rambhau D, Apte SS, Gopinath D. 1-O-alkylglycerol stabilized carbamazepine intraveinous o/w nanoemulsions for drug targeting in mice. J. Drug Targeting. 2007;15:154–161.
    1. Osmond DG, Roylance PJ, Webb AJ, Yoffey JM. The action of batyl alcohol and selachyl alcohol on the bone marrow of guinea pig. Acta Haemat. 1963;29:180–186.
    1. Linman JW. Hematopoietic effects of glyceryl ethers. III. Inactivity of selachyl alcohol. Proc. Soc. Exp. Biol. Med. 1960;104:703–706.
    1. Denizot Y, Guglielmi L, Donnard M, Trimoreau F. Platelet-activating factor and normal and leukaemic haematopoiesis. Leuk. Lymphoma. 2003;44:775–782.
    1. Dupuis F, Levasseur S, Jean-Louis F, Dulery C, Praloran V, Denizot Y, Michel L. Production, metabolism and effect of platelet-activating factor on the growth of the human K562 cell line. Bichim. Biophys. Acta. 1997;1359:241–249.
    1. Yamamoto N, Ngwenya BZ, Sery TW, Pieringer RA. Activation of macrophages by ether analogues of lysophospholipids. Cancer Immunol. Immunother. 1987;25:185–192.
    1. Yamamoto N, St Claire DA, Jr, Homma S, Ngwenya BZ. Activation of mouse macrophages by alkylglycerols, inflammation products of cancerous tissues. Cancer Res. 1988;48:6044–6049.
    1. Pédrono F, Khan NA, Legrand AB. Regulation of calcium signalling by 1-O-alkylglycerols in human Jurkat T cells. Life Sci. 2004;74:2793–2801.
    1. Lee J-K, Back TC, Komschlies KL, Ruscetti FW, Young HA, Wiltrout RH. Hematopoietic switch from lymphoid to granulocytic development in 3LL tumor-bearing mice. In Vivo. 2001;15:255–264.
    1. Shin-Ya M, Mazda O, Tsuchihara C, Hirai H, Imanishi J, Takeuchi M. Interleukin-2 abolishes myeloid cell accumulation induced by Lewis lung carcinoma. J. Interferon Cytokine Res. 2003;23:631–638.
    1. Al-Darmaki S, Knightshead K, Ishihara Y, Best A, Schenkein HA, Tew JG, Barbour SE. Delineation of the role of platelet-activating factor in the immunoglobulin G2 antibody response. Clin. Diagn. Lab. Immunol. 2004;4:720–728.
    1. Matsumura Y, Byrne SN, Nghiem DX, Miyahara Y, Ullrich SE. A role for inflammatory mediators in the induction of immunoregulatory B cells. J. Immunol. 2006;177:4810–4817.
    1. Houck KL, Fox TE, Sandirasegarane L, Kester M. Ether-linked diglycerides inhibit vascular smooth muscle cell growth via decreased MAPK and PI3K/Akt signalling. Am. J. Physiol. 2008;295:1657–1668.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi