Cell Biochemistry and Biophysics

, Volume 64, Issue 1, pp 45–59 | Cite as

Chemical–Physical Changes in Cell Membrane Microdomains of Breast Cancer Cells After Omega-3 PUFA Incorporation

  • Paola A. Corsetto
  • Andrea Cremona
  • Gigliola Montorfano
  • Ilaria E. Jovenitti
  • Francesco Orsini
  • Paolo Arosio
  • Angela M. Rizzo
Original Paper

Abstract

Epidemiologic and experimental studies suggest that dietary fatty acids influence the development and progression of breast cancer. However, no clear data are present in literature that could demonstrate how n − 3 PUFA can interfere with breast cancer growth. It is suggested that these fatty acids might change the structure of cell membrane, especially of lipid rafts. During this study we treated MCF-7 and MDA-MB-231 cells with AA, EPA, and DHA to assess if they are incorporated in lipid raft phospholipids and are able to change chemical and physical properties of these structures. Our data demonstrate that PUFA and their metabolites are inserted with different yield in cell membrane microdomains and are able to alter fatty acid composition without decreasing the total percentage of saturated fatty acids that characterize these structures. In particular in MDA-MB-231 cells, that displays the highest content of Chol and saturated fatty acids, we observed the lowest incorporation of DHA, probably for sterical reasons; nevertheless DHA was able to decrease Chol and SM content. Moreover, PUFA are incorporated in breast cancer lipid rafts with different specificity for the phospholipid moiety, in particular PUFA are incorporated in PI, PS, and PC phospholipids that may be relevant to the formation of PUFA metabolites (prostaglandins, prostacyclins, leukotrienes, resolvines, and protectines) of phospholipids deriving second messengers and signal transduction activation. The bio-physical changes after n − 3 PUFA incubation have also been highlighted by atomic force microscopy. In particular, for both cell lines the DHA treatment produced a decrease of the lipid rafts in the order of about 20–30 %. It is worth noticing that after DHA incorporation lipid rafts exhibit two different height ranges. In fact, some lipid rafts have a higher height of 6–6.5 nm. In conclusion n − 3 PUFA are able to modify lipid raft biochemical and biophysical features leading to decrease of breast cancer cell proliferation probably through different mechanisms related to acyl chain length and unsaturation. While EPA may contribute to cell apoptosis mainly through decrease of AA concentration in lipid raft phospholipids, DHA may change the biophysical properties of lipid rafts decreasing the content of cholesterol and probably the distribution of key proteins.

Keywords

EPA DHA AA PUFA Breast cancer Lipid rafts Phospholipids Membrane 

Abbreviations

PLs

Phospholipids

FA

Fatty acids

PUFA

Polyunsaturated fatty acids

MUFA

Monounsaturated fatty acids

SFA

Saturated fatty acids

DHA

Docosahexaenoic acid

EPA

Eicosapentaenoic acid

AA

Arachidonic acid

PE

Phosphatidylethanolamine

PI

Phosphatidylinositol

PC

Phosphatidylcholine

PS

Phosphatidylserine

SM

Sphingomyelin

Chol

Cholesterol

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Paola A. Corsetto
    • 1
  • Andrea Cremona
    • 1
  • Gigliola Montorfano
    • 1
  • Ilaria E. Jovenitti
    • 1
  • Francesco Orsini
    • 2
  • Paolo Arosio
    • 2
  • Angela M. Rizzo
    • 1
  1. 1.Dipartimento di Scienze Farmacologiche e BiomolecolariUniversità degli Studi di MilanoMilanItaly
  2. 2.Dipartimento di FisicaUniversità degli Studi di MilanoMilanItaly

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