Therapeutic Potential of Membrane Fatty Acid Modifiaction in Tumor Cells

  • Shon, Yun-Hee ;
  • Park, Kun-Young ;
  • Kim, Kwang-Soo
  • Published : 1996.06.01


The membrane fatty acid composition of tumor cell can be modified either in cell by altering the lipid composition of the medium of during growth in animals by changing the dietaty fat composition. These modifications are associated with changes in membrane physical properties and certain cellular functions, including carrier-mediated transport and enzyme contained within the membrane. Such effects influence the transport of nutrients and chemotherapeutic agents in cancer cells .Fatty acid modification also can enhance the sensitivity of the neoplastic cell to chemotherapy. The alteration in plasma membrane composition will be affected through dietary supplementations and the potential value to cancer patients could be a better understanding of the effects of diet on responsiveness of neoplasms to chemotherapy, i.e. cancer patients' chances for a "cure" can be improved by diet changes prior to treatment.


membrane fatty acid;tumor cell;dietary modification;chemotherapy


  1. Science v.160 Fatty-acid composition of mycoplasma lipids : biomembrane with only one fatty acid Tanaka,S.;Sakamoto,K.;Takagi,J.;Tsuchimoto,M.
  2. Science v.164 Mycoplasma membrane lipids : variations in fatty acid composition McElhaney,R.N.;Tourtellotte,M.E.
  3. Proc. Natl. Acad. Sci. U.S.A. v.71 Regulation of the fatty acid composition of the membrane phospholipids of Escherichia coli Cronan,Jr.J.E.
  4. Biochim. Biophys. Acta v.373 Changes in cell permeability following a marked reduction of saturated fatty acid content of Escherichia coli K-12 Davis,M.B.;Silbert,D.F.
  5. Biochem. J. v.146 Membrane-lipid unsaturation and mitochondrial function in Saccharomyces cerevisiae Watson,K.;Houghton,R.L.;Bertoli,E.;Griffiths,D.E.
  6. Cancer Res. v.27 The importance of free fatty acid in tumor nutrition Spector,A.A.
  7. J. Lipid Res. v.15 Flux of free fatty acids among host tissues, ascites fluid, and Ehrlich ascites carcinoma cells Mermier,P.;Baker,N.
  8. J. Biol. Chem. v.242 Turnover and utilization of esterified fatty acids in Ehrlich ascites tumor cells Spector,A.A.;Steinberg,D.
  9. Biochim. Biophys. Acta v.426 Modification of the fatty acid composition of Ehrlich ascites tumor cell plasma membranes Awad,A.B.;Spector,A.A.
  10. Biochim. Biophys. Acta v.311 Membrane lipid fatty acids and regulation of membrane-bound enzymes. Allosteric behavior of erythrocyte Mg²+-ATPase, (Na²+K²)-ATPase and acetylcholinesterase from rats fed different fat-supplemented diets Bloj,B.;Morero,R.D.;Farias,R.N.;Trucco,R.E.
  11. Proc. Natl. Acad. Sci. U.S.A. v.73 Modification of adenylate cyclase activity in LM cells by manipulation of the membrane phospholipid composition in vivo Engelhard,V.H.;Esko,J.D.;Storm,D.R.;Glaser,M.
  12. J. Natl. Cancer Inst. v.56 Enhanced growth rate of transplanted mammary adenocarcinoma induced in C3H mice by dietary linoleate Rao,G.A.;Abraham,S.
  13. Lipids v.10 Hepatoma, host liver, and normal rat liver phospholipids as affected by diet Wood,R.
  14. J. Biol. Chem. v.253 Effect of specific fatty acid enrichments on membrane physical properties detected with a spin label probe King,M.E.;Spector,A.A.
  15. J. Neurochem. v.40 Glycine uptake by cultured human Y79 retinoblastoma cells. Effect of changes in phospholipid fatty acid unsaturation Yorek,M.A.;Hyman,B.T.;Spector,A.A.
  16. Prostaglandins Leukot. Med. v.30 Fatty acid modification of cultured neuroblastoma cells by gamma linolenic acid relevant to its antitumor effect Fujiwara,F.;Todo,S.;Imashuku,S.
  17. J. Natl. Cancer Inst. v.81 Growth inhibition effects of oleic acid, linoleic acid and their methyl esters on transplanted tumors in mice Zhu,Y.P.;Su,Z.W.;Li,C.H.
  18. MS thesis, Pusan National University Antimutagenic and anticancerigenic effects of linoleic acid Lim,S.Y.
  19. J. Cell Physiol. v.123 1 α, 25-dihydroxy vitamin D₃ specific regulation of growth, morphology and fibronectin in a human osteosarcoma cell line Franceschi,R.T.;James,W.M.;Zerlauth,G.
  20. Biochemistry v.16 Diet-induced changes in plasma membrane fatty acid composition affect physical properties detected with a spin-label probe King,M.E.;Stavens,B.W.;Spector,A.A.
  21. Fed. Proc. v.35 Mechanism of anion transport in red blood cells : role of membrane proteins Rothstein,A.;Cabantchik,Z.I.;Knauf,P.
  22. Biochim. Biophys. Acta v.300 Membrane-bound enzymes and membrane ultrastructure Coleman,R.
  23. Biochemistry v.13 Reversible lipid titrations of the activity of pure adenosine triphosphatase-lipid complexes Warren,G.B.;Toon,P.A.;Birdsall,N.J.M.;Lee,A.G.;Metcalfe,J.C.
  24. Biochim. Biophys. Acta v.394 Polar head-group and acyl side-chain requirements for phospholipid-dependent ($Na^{-}+K^{+}$)-ATPase Walker,J.A.;Wheeler,K.P.
  25. J. Biol. Chem. v.251 Effect of lipids on the reconstitution of D-lactate oxidase in Escherichia coli membrane vesicles George-Nascimento,C.;Wakil,S.J.;Short,S.A.;Kaback,H.R.
  26. Biochemistry v.15 Changes in (Na¹+K¹)-ATPase activity of Ehrlich ascites tumor cells cells produced by alteration of membrane fatty acid composition Solomonson,L.P.;Liepkalns,V.A.;Spector,A.A.
  27. Experimental and clinical progress in cancer chemotherapy Cell surface membranes as a chemotherapeutic target Tritton,T.R.;Hickman,J.A.;Muggia,F.M.(ed.)
  28. Science v.217 The anticancer agent adriamycin can be actively cytotoxic without entering cells Tritton,T.R.;Lee,G.
  29. Cancer Treat. Rep. v.68 Differences in lipid composition of doxorubicin-sensitive and -resistant P388 cells Ramu,A.;Glaubiger,D.;Weintraub,H.
  30. Biochim. Biophys. Acta v.649 Adriamycin-induced changes in the surface membrane of sarcoma 180 ascites cells Murphree,S.A.;Tritton,T.R.;Smith,P.L.;Sartorelli,A.C.
  31. Cancer Res. v.44 Effect of cellular fatty acid alteration on adriamycin sensitivity in cultured L1210 murine leukemia cells Guffy,M.M.;North,J.A.;Burns,C.P.
  32. J. Clin. Invest. v.74 Dietary menhaden oil lowers plasma prostaglandins and calcium in mice bearing the prostaglandin-producing HSDM₁ fibrosarcoma Tashjian,A.H.;Voelkel,E.F.;Robinson,D.R.;Levine,L.
  33. J. Neurochem. v.38 Choline uptake in cultured human Y79 retinoblastoma cells : effect of polyunsaturated fatty acid compositional modifications Hyman,B.T.;Spector,A.A.
  34. Lipids v.12 Diet-induced changes in the fatty acid composition of mouse hepatocyte plasma membranes Hopkins,G.J.;West,C.E.
  35. Biochem. Biophys. Res. Commun. v.63 Alteration of the fatty acid composition of Ehrlich ascites tumor cell lipids Liepkalns,V.A.;Spector,A.A.
  36. Cancer Res. v.39 Effect of modification of plasma membrane fatty acid composition on fluidity and methotrexate transport in L1210 murine leukemila cells Burns,C.P.;Luttenegger,D.G.;Dudley,D.T.;Buettner,G.R.;Spector,A.A.
  37. Cancer Res. v.43 Plasma membrane lipid structural order in doxorubicin-sensitive and -resistant P388 cells Ramu,A.;Glaubiger,D.;Magrath,I.T.;Joshi,A.
  38. J. Biol. Chem. v.253 Similarities in the membrane fluidity of 3T3 and SV101-3T3 cells and its relation to concanavalin A- and wheat germ agglutinin-induced agglutination Hatten,M.E.;Scandella,C.J.;Horwitz,A.F.;Burger,M.M.
  39. Biochim. Biophys. Acta v.415 Regulation of allosteric membrane-bound enzymes through changes in membrane lipid composition Farias,R.N.;Bloj,B.;Morero,R.D.;Sineriz,F.;Trucco,R.E.
  40. Science v.224 Reversal of adriamycin resistance by verapamil in human ovarian cancer Rogan,A.M.;Hamilton,T.C.;Young,R.C.;Klecker,R.W.;Ozols,R.F.
  41. Cancer Res. v.42 Effect of cellular fatty acid alteration on hyperthermic sensitivity in cultured L1210 murine leukemia cells Guffy,M.M.;Rosenberger,J.A.;Simon,I.;Burns,C.P.
  42. J. Lipid Res. v.15 Utilization of ascites plasma very low density lipoprotein triglycerides by Ehrlich cells Brenneman,D.E.;Spector,A.A.
  43. J. Biol. Chem. v.251 Role of phospholipids in the calcium-dependent ATPase of the sarcoplasmic reticulum Hidalgo,C.;Ikemoto,N.;Gergely,J.
  44. J. Neurochem. v.42 Effect of membrane polyunsaturation on carrier-mediated transport in cultured retinoblastoma cells Alterations in taurine uptake Yorek,M.A.;Strom,D.K.;Spector,A.A.
  45. Biochim. Biophys. Acta v.888 Adriamycin transport and sensitivity in fatty acid-modified leukemia cells Burns,C.P.;North,J.A.
  46. J. Biol. Chem. v.252 Effect of fatty acid saturation on α-aminoisobutyric acid transport in Ehrlich ascites cells Kaduce,T.L.;Awad,A.B.;Fontenelle,L.J.;Spector,A.A.