Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase protein expression using reverse-phase protein microarrays

  • Authors:
    • Javier A. Menendez
    • Alejandro Vazquez-Martin
    • Cristina Oliveras-Ferraros
    • Rocio Garcia-Villalba
    • Alegria Carrasco-Pancorbo
    • Alberto Fernandez-Gutierrez
    • Antonio Segura-Carretero
  • View Affiliations

  • Published online on: October 1, 2008     https://doi.org/10.3892/ijmm_00000039
  • Pages: 433-439
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Abstract

Inhibitors of fatty acid synthase (FASN), a key enzyme involved in the anabolic conversion of dietary carbohydrates to fat in mammals, are receiving increasingly more attention as they may provide therapeutic moieties for the treatment of human malignancies. Natural compounds, such as the green tea polyphenol epigallocatechin-3-gallate, have been shown to induce anti-cancer effects by suppressing FASN, which may account for the epidemiologically observed inverse correlation between green-tea drinking and cancer risk in Oriental populations. Since extra-virgin olive oil (EVOO)-derived phenolics have been suggested to possess biological activities that may explain the health-promoting effects of the ‘Mediterranean diet’, we evaluated their effects on the expression of FASN protein in human breast epithelial cell lines. First, we developed a reverse phase protein microspot array (RPPA) capable of rapidly assessing the relative amount of FASN protein in whole lysates from cultured human cells. Then we tested the effects of phenolic fractions from EVOO and its main constituents including single phenols (i.e. tyrosol, hydroxytyrosol, vanillin), phenolic acids (i.e. caffeic acid, p-coumaric acid, vanillic acid, ferulic acid, elenolic acid), lignans (i.e. 1-[+]-pinoresinol, 1-[+]-acetoxy-pinoresinol), flavonoids (i.e. apigenin, luteolin), or secoiridoids (i.e. deacetoxyoleuropein aglycone, ligstroside aglycone, oleuropein glycoside, oleuropein aglycone) on FASN protein expression. EVOO polyphenols lignans, flavonoids and secoiridoids were found to drastically suppress FASN protein expression in HER2 gene-amplified SKBR3 breast cancer cells. Equivalent results were observed in MCF-7 cells engineered to overexpress the HER2 tyrosine kinase receptor, a well-characterized up-regulator of FASN expression in aggressive sub-types of cancer cells. EVOO-derived lignans, flavonoids and secoiridoids were significantly more effective than the mono-HER2 inhibitor trastuzumab (≈50% reduction) and as effective as the dual HER1/HER2 tyrosine kinase inhibitor lapatinib (≥95% reduction) at suppressing high-levels of FASN protein in HER2-overexpressing SKBR3 and MCF-7/HER2 cells. EVOO single phenols and phenolic acids failed to modulate FASN expression in SKBR3 and MCF-7/HER2 cells. These findings reveal for the first time that phenolic fractions, directly extracted from EVOO, may induce anti-cancer effects by suppressing the expression of the lipogenic enzyme FASN in HER2-overexpressing breast carcinoma cells, thus offering a previously unrecognized mechanism for EVOO-related cancer preventive effects.

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October 2008
Volume 22 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Menendez JA, Vazquez-Martin A, Oliveras-Ferraros C, Garcia-Villalba R, Carrasco-Pancorbo A, Fernandez-Gutierrez A and Segura-Carretero A: Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase protein expression using reverse-phase protein microarrays. Int J Mol Med 22: 433-439, 2008.
APA
Menendez, J.A., Vazquez-Martin, A., Oliveras-Ferraros, C., Garcia-Villalba, R., Carrasco-Pancorbo, A., Fernandez-Gutierrez, A., & Segura-Carretero, A. (2008). Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase protein expression using reverse-phase protein microarrays. International Journal of Molecular Medicine, 22, 433-439. https://doi.org/10.3892/ijmm_00000039
MLA
Menendez, J. A., Vazquez-Martin, A., Oliveras-Ferraros, C., Garcia-Villalba, R., Carrasco-Pancorbo, A., Fernandez-Gutierrez, A., Segura-Carretero, A."Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase protein expression using reverse-phase protein microarrays". International Journal of Molecular Medicine 22.4 (2008): 433-439.
Chicago
Menendez, J. A., Vazquez-Martin, A., Oliveras-Ferraros, C., Garcia-Villalba, R., Carrasco-Pancorbo, A., Fernandez-Gutierrez, A., Segura-Carretero, A."Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase protein expression using reverse-phase protein microarrays". International Journal of Molecular Medicine 22, no. 4 (2008): 433-439. https://doi.org/10.3892/ijmm_00000039