Abstract
Simple SummaryBreast cancer is a disease influenced by dietetic factors, such as the type and amount of lipids in a diet. In this work, we aimed to elucidate the different effects of two high-fat diets on the histopathological and molecular characteristics of mammary tumors in an experimental model. Animals fed with a diet high in extra-virgin olive oil (EVOO), compared to those fed with a diet high in seed oil, developed tumors with less aggressiveness and proliferation. Tumor molecular analyses of several cell death pathways also suggested an effect of EVOO in this process. In vitro experiments indicated the role of EVOO minor compounds on the effects of this oil. Obtaining insights into the influence and the mechanisms of action of dietary compounds are necessary to understand the relevance that dietetic habits from childhood may have on health and the risk of disease.Breast cancer is the most common malignancy among women worldwide. Modifiable factors such as nutrition have a role in its etiology. In experimental tumors, we have observed the differential influence of high-fat diets in metabolic pathways, suggesting a different balance in proliferation/apoptosis. In this work, we analyzed the effects of a diet high in n-6 polyunsaturated fatty acids (PUFA) and a diet high in extra-virgin olive oil (EVOO) on the histopathological features and different cell death pathways in the dimethylbenz(a)anthracene-induced breast cancer model. The diet high in n-6 PUFA had a stimulating effect on the morphological aggressiveness of tumors and their proliferation, while no significant differences were found in groups fed the EVOO-enriched diet in comparison to a low-fat control group. The high-EVOO diet induced modifications in proteins involved in several cell death pathways. In vitro analysis in different human breast cancer cell lines showed an effect of EVOO minor compounds (especially hydroxytyrosol), but not of fatty acids, decreasing viability while increasing apoptosis. The results suggest an effect of dietary lipids on tumor molecular contexts that result in the modulation of different pathways, highlighting the importance of apoptosis in the interplay of survival processes and how dietary habits may have an impact on breast cancer risk.
Highlights
Breast cancer is the most common cancer in women worldwide, with high incidence, prevalence, and mortality rates [1]
We have studied proteins involved in the apoptotic intrinsic pathway: the proapoptotic Bid and the active tBid, Bak, Bax, Cytochrome C in mitochondrial and cytoplasm fraction, APAF, pro-Caspase-9, cleaved-Caspase-9, and the anti-apoptotic Bcl2 (Figure 3 and Original Western blots in Supplementary material)
There was a trend in the HCO group to have lower levels of pro-Caspase-12, while a trend to have higher levels of the active cleaved form was observed in the LF-HCO group
Summary
Breast cancer is the most common cancer in women worldwide, with high incidence, prevalence, and mortality rates [1] This neoplasia has a multifactorial etiology, in which diet, as an environmental factor, has an important role. Regarding monounsaturated fatty acids (MUFA), evidence is still uncertain, and experimental studies have described effects ranging from a weak promoting effect to a protective effect on mammary carcinogenesis [4]. In this sense, the Mediterranean diet, of which a main source of fat is olive oil (rich in the n-9 MUFA oleic acid), is considered a healthy dietary pattern, with beneficial effects on the risks of cardiovascular diseases, obesity, and cancer. Epidemiological studies have demonstrated that adherence to this diet is associated to a reduction of overall and cancer mortality [5,6,7]
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