Olive oil and omega-3 polyunsaturated fatty acids suppress intestinal polyp growth by modulating the apoptotic process in ApcMin/+ mice

Abstract

The promotion and progression of carcinogenesis are susceptible to nutritional interventions aimed at counteracting cancer development. Lipid metabolism is essential in the onset and progression of tumors and for cancer cell survival. In this study, we tested the effects of diets enriched with natural compounds, such as olive oil and salmon oil, in mice that spontaneously develop intestinal polyps (Apc(Min/+) mice). For this purpose, we evaluated polyp number and volume, intestinal mucosa proliferation/apoptosis, estrogen receptors (ERs) expression, fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase gene expression and enzymatic activity. Compared with the standard diet, the salmon oil-enriched diet, containing a high percentage of omega-3 polyunsaturated fatty acids, and, to a lesser extent, olive oil-enriched diet reduced polyp number and volume through a reduction of proliferation and a marked proapoptotic effect. These biological effects were mediated by an inhibition of fatty acid synthase and HMGCoA reductase gene expression and activity and an increase of ERβ/ERα ratio. Our findings suggest that a proper dietary lifestyle could contribute to primary cancer prevention.

Olive oil prevents benzo(a)pyrene [B(a)P]-induced colon carcinogenesis through altered B(a)P metabolism and decreased oxidative damage in ApcMin mouse model

“…There were no differences in polyp number and size in control [tricaprylin-vehicle for B(a)P and olive oil alone] mice. Similar to our observation, Barone et al [47] also found that olive oil-enriched diet reduced the spontaneously developed tumors in the colon to a minor extent. Overall, our findings demonstrate that mice that were treated with B(a)P + olive oil resulted in a decrease in the incidence, size and number of adenomas formed in the colon.…”

Dietary Methyl Donor Depletion Suppresses Intestinal Adenoma Development

“…These findings suggest that elevated basal proliferation of normal gut mucosa may be an important early and predisposing factor in cancer development. As reviewed by Tammariello and Milner (43), a large number of dietary agents have been tested for their chemopreventive benefit in Apc mouse models; among the most effective cancer prevention strategies are those agents that target cell proliferation rates within morphologically normal, but at-risk mucosa (44,45). As discussed by Kim (46), folate restriction alone has the ability to reduce basal proliferation rates in animal tumor models.…”

Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic ApcMin/+ Mice, Correlating with CB1 Receptor Up-Regulation

“…In vivo experiments were carried out as previously described [4]. Briefly, Apc Min/+ transgenic mice (five-weeks-old), were purchased from Charles River (Calco, CO, Italy) and maintained in controlled conditions and with a free access to food and water.…”

“…Centre Inc., Cincinnati, OH, USA), was reverse transcripted in 20 μL of the final volume at 41 °C for 60 min, using 30 pmol antisense primer for CB1 receptor and β-actin gene (Table 2). Real-time PCR was carried out as previously described [4]. All expression data were normalized by dividing the target amount by the amount of β-actin , used as internal control.…”

“…PUFAs can inhibit colon carcinogenesis, affecting tumor progression [3]. Previously, we showed the ability of ω-3 PUFAs to arrest cell growth and to promote cell apoptosis in animal and in vitro studies [4,5,6]. Moreover, ω-3 PUFAs ingested in the diet were also able to significantly reverse polyp development in Apc Min/+ mice through inducing the estrogen receptor β and Low Density Lipoprotein (LDL) receptor [7], known to be negative modulators of cell proliferation.…”