European Journal of Nutrition

, Volume 56, Issue 2, pp 509–519 | Cite as

Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis

  • Marianela Vara-Messler
  • Maria E. Pasqualini
  • Andrea Comba
  • Renata Silva
  • Carola Buccellati
  • Annalisa Trenti
  • Lucia Trevisi
  • Aldo R. Eynard
  • Angelo Sala
  • Chiara Bolego
  • Mirta A. Valentich
Original Contribution



The aim of this study was to determine whether α-linolenic acid (ALA ω-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma.

Materials and methods

BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA ω-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma.


After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from ω-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) α expression, a recognized breast cancer promotor while showing an opposite effect on ERβ in tumor lysates.


These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention.


α-linolenic acid (ALA) Chia oil Mammary carcinoma LOXs metabolites Estrogen receptor 



We are indebted to Mr. Ricardo Mattos (Instituto de Biologìa Celular, FCM-UNC) for animal care, Gina Madzzudulli (INICSA-CONICET) for immunohistochemistry, and Andrea Pagetta (PhD) for technical assistance with the microscope analysis (University of Padua). We also thank to Martin Fernandez-Zapico (MD) for critical review. Prof. Mirta A. Valentich acknowledges the support from Ministerio de Ciencia y Tecnología de Córdoba, Argentina (MINCYT) Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SECyT-UNC) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Prof. Chiara Bolego and Lucia Trevisi (PhD) acknowledge the support from institutional funding of the University of Padova.

Compliance with ethical standards

Conflict of interest

The author states that there is no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

394_2015_1096_MOESM1_ESM.pdf (24 kb)
Supplementary material 1 (PDF 23 kb)
394_2015_1096_MOESM2_ESM.pdf (1 mb)
Supplementary material 2 (PDF 1047 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Marianela Vara-Messler
    • 1
    • 2
    • 3
  • Maria E. Pasqualini
    • 1
    • 2
  • Andrea Comba
    • 1
    • 2
  • Renata Silva
    • 1
    • 2
  • Carola Buccellati
    • 4
  • Annalisa Trenti
    • 3
  • Lucia Trevisi
    • 3
  • Aldo R. Eynard
    • 1
    • 2
  • Angelo Sala
    • 4
    • 5
  • Chiara Bolego
    • 3
  • Mirta A. Valentich
    • 1
    • 2
  1. 1.Instituto de Investigaciones en Ciencias de la Salud de Córdoba (INICSA-CONICET)Universidad Nacional de CórdobaCórdobaArgentina
  2. 2.Instituto de Biología Celular, Cátedra de Biología Celular, Histología y Embriología, Facultad de Ciencias MédicasUniversidad Nacional de CórdobaCórdobaArgentina
  3. 3.Department of Pharmaceutical and Pharmacological SciencesUniversity of PaduaPaduaItaly
  4. 4.Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
  5. 5.Institute of Biomedicine and Molecular ImmunologyItalian National Research CouncilPalermoItaly

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