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Published on: March 17, 2016
Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase protein
Javier A Menendez1, Alejandro Vazquez-Martin, Cristina Oliveras-Ferraros
1Girona Biomedical Research Institute, Medical Oncology, Dr. Josep Trueta University Hospital of Girona, E-17007 Girona, Catalonia, Spain. jmenendez@ico.scs.es
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 ( approximately 50% reduction) and as effective as the dual HER1/HER2 tyrosine kinase inhibitor lapatinib (> or =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.
Insights
Extra-virgin olive oil polyphenols, specifically lignans, flavonoids, and secoiridoids, significantly suppress fatty acid synthase (FASN) in HER2-overexpressing breast cancer cells. These EVOO compounds show potent anti-cancer effects by inhibiting FASN, offering a new mechanism for olive oil
Area of Science:
- Oncology
- Nutritional Biochemistry
- Molecular Biology
Background:
- Fatty acid synthase (FASN) is a key enzyme in lipogenesis, crucial for cancer cell proliferation.
- Inhibitors of FASN are investigated as potential anti-cancer therapeutics.
- Extra-virgin olive oil (EVOO) phenolics are linked to health benefits, including cancer prevention.
Purpose of the Study:
- To investigate the effects of EVOO-derived phenolics on FASN protein expression in human breast cancer cell lines.
- To evaluate the potential of EVOO components as therapeutic agents against HER2-overexpressing breast cancers.
Main Methods:
- Development of a reverse phase protein microspot array (RPPA) for FASN protein quantification.
- Treatment of HER2-amplified SKBR3 and HER2-overexpressing MCF-7 breast cancer cells with EVOO phenolic fractions and constituents.
- Comparison of EVOO compounds' efficacy with HER2-targeted therapies (trastuzumab, lapatinib).
Main Results:
- EVOO-derived lignans, flavonoids, and secoiridoids significantly suppressed FASN protein expression in SKBR3 and MCF-7/HER2 cells.
- These EVOO polyphenols were more effective than trastuzumab and as effective as lapatinib in reducing FASN levels.
- EVOO single phenols and phenolic acids did not modulate FASN expression.
Conclusions:
- EVOO phenolic fractions, particularly lignans, flavonoids, and secoiridoids, exhibit anti-cancer properties by inhibiting FASN in HER2-overexpressing breast cancer.
- These findings suggest a novel mechanism for the cancer-preventive effects of EVOO consumption.
- EVOO-derived compounds represent a promising natural source for developing novel anti-cancer strategies.
