, Volume 15, Issue 1–3, pp 31–50 | Cite as

Diverse effects of essential (n−6 andn−3) fatty acids on cultured cells

  • Stephanos I. Grammatikos
  • Papasani V. Subbaiah
  • Thomas A. Victor
  • William M. Miller


Fatty acids (FAs) have long been recognized for their nutritional value in the absence of glucose, and as necessary components of cell membranes. However, FAs have other effects on cells that may be less familiar. Polyunsaturated FAs of dietary origin (n−6 andn−3) cannot be synthesized by mammals, and are termed ‘essential’ because they are required for the optimal biologic function of specialized cells and tissues. However, they do not appear to be necessary for normal growth and metabolism of a variety of cells in culture. The essential fatty acids (EFAs) have received increased attention in recent years due to their presumed involvement in cardiovascular disorders and in cancers of the breast, pancreas, colon and prostate. Manyin vitro systems have emerged which either examine the role of EFAs in human disease directly, or utilize EFAs to mimic thein vivo cellular environment. The effects of EFAs on cells are both direct and indirect. As components of membrane phospholipids, and due to their varying structural and physical properties, EFAs can alter membrane fluidity, at least in the local environment, and affect any process that is mediated via the membrane. EFAs containing 20 carbons and at least three double bonds can be enzymatically converted to eicosanoid hormones, which play important roles in a variety of physiological and pathological processes. Alternatively, EFAs released into cells from phospholipids can act as second messengers that activate protein kinase C. Furthermore, susceptibility to oxidative damage increases with the degree of unsaturation, a complication that merits consideration because lipid peroxidation can lead to a variety of substances with toxic and mutagenic properties. The effects of EFAs on cultured cells are illustrated using the responses of normal and tumor human mammary epithelial cells. A thorough evaluation of EFA effects on commercially important cells could be used to advantage in the biotechnology industry by identifying EFA supplements that lead to improved cell growth and/or productivity.

Key words

Desaturation eicosanoids lipid peroxidation membrane fluidity protein kinase C serum-free medium 



arachidonic acid (20 carbons: 4 double bonds,n−6)


butylated hydroxyanisole


butylated hydroxytoluene


cyclic adenosine monophosphate


Chinese hamster ovary




dihomo-γ-linolenic acid (20∶3,n−6)


docosahexaenoic acid (22∶6,n−3)


essential fatty acid


epidermal growth factor


epidermal growth factor receptor


eicosapentaenoic acid (20∶5,n−3)


fatty acid


fetal bovine serum


γ-linolenic acid (18∶3,n−6)


linoleic acid (18∶2,n−6)


α-linolenic acid (18∶3,n−3)






nicotinamide adenine dinucleotide


nordihydroguaiaretic acid


oleic acid (18∶1,n−9)




protein kinase C


polyunsaturated fatty acid


serum-free medium




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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Stephanos I. Grammatikos
    • 1
  • Papasani V. Subbaiah
    • 2
  • Thomas A. Victor
    • 3
  • William M. Miller
    • 1
  1. 1.Department of Chemical EngineeringNorthwestern UniversityEvanstonUSA
  2. 2.Departments of Biochemistry and MedicineRush Medical CollegeChicagoUSA
  3. 3.Department of PathologyNorthwestern University Medical School, Evanston HospitalEvanstonUSA

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