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

Notarnicola, Maria; Tutino, Valeria; Nunzio, Valentina De; Dituri, Francesco; Caruso, Maria Gabriella; Giannelli, Gianluigi

doi:10.3390/ijms18030485

Cited by 23 publications

(20 citation statements)

References 30 publications

(33 reference statements)

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“…Previously, we have demonstrated that tumor-associated factors, such as cytokines, growth factors or cellular receptors can influence lipid metabolism in peritumoral adipose tissue [ 24 ]. Moreover, in an animal model of colon carcinogenesis, we demonstrated that cancer cell metabolism is affected by dietary natural compounds, which are able to control and to improve the environmental conditions where tumors develop [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Metastatic CRC patients showed significantly lower percentage of EPA, an n -3-PUFA, known for its efficacy in regulating the lipid metabolism and for its anti-proliferative effects in vitro and in vivo [ 13 , 25 , 26 ]. EPA has been demonstrated to exert anti-proliferative effects through the regulation of HMGCoA reductase gene expression and of lipogenic enzymes belonging to the cholesterol biosynthetic pathway [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

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Differential Tissue Fatty Acids Profiling between Colorectal Cancer Patients with and without Synchronous Metastasis

Notarnicola

Lorusso

Tutino

et al. 2018

IJMS

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The early detection of colorectal cancer and determination of its metastatic potential are important factors to set up more efficacious therapeutic strategies. In the present study, we hypothesize that fatty acids analysis in colorectal cancer patients can discriminate between metastatic and non-metastatic patients. Fifty-one consecutive patients with histologically proven colorectal cancer were enrolled in the study and the presence of synchronous metastasis was detected in 25 of these 51 patients. Fatty acid profile analysis in red blood cell membranes was not able to discriminate the metastatic colorectal cancer patients from those without metastasis. However, significant differences in the tumor tissue fatty acid profile were found in metastatic cancer patients when compared to patients without metastasis. Metastatic patients showed significantly lower percentages of Eicosapentaenoic acid (EPA) and higher levels of γ-linolenic acid (GLA), a n-3- and n-6-Polyunsaturated fatty acid (PUFA), respectively. Our findings, suggesting that membrane lipid rearrangement could influence the cellular function and make the cell more prone to metastasis, offer the opportunity to develop nutritional strategies that may be helpful in the prevention and treatment of colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential Tissue Fatty Acids Profiling between Colorectal Cancer Patients with and without Synchronous Metastasis

Notarnicola

Lorusso

Tutino

et al. 2018

IJMS

Self Cite

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“…Different markers and signaling pathways involved in the development and progression of these cancers have been shown to be negatively regulated by omega-3 PUFA, including those involved in apoptosis and cell proliferation [ 13 , 14 , 15 ]. In particular, plenty of studies performed both in vitro and in vivo in different kinds of cancer have demonstrated the ability of these fatty acids to inhibit cell proliferation and induce apoptosis [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ] These fatty acids have been However, some positive associations were recently found between the incidence/progression of human prostate cancer and high levels of intake or high concentrations of these fatty acids (FA) in blood or prostate tissue [ 25 ]. Even though other factors (such as individual genetic profiles or carcinogenic contaminants present in the dietary sources of these FA) may be more directly involved in prostate carcinogenesis [ 11 ], the alarming positive associations prompted to suggest that extremely high levels of omega-3 PUFA intake should be avoided.…”

Section: Introductionmentioning

confidence: 99%

Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

Serini

Cassano

Corsetto

et al. 2018

IJMS

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New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC), one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA). These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN) having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.

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“…Dietary enrichment with ω-3 LCPUFAs such as DHA and EPA present in fish oil and certain plant and nut oils [ 2 , 20 , 21 ] has been shown to protect against inflammation [ 22 , 23 ], pathological angiogenesis [ 24 ], and tumorigenesis [ 25 – 31 ]. We have previously shown that leukocyte recruitment to and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs, and that 17,18-epoxyeicosatetraenoic acid (EEQ) and 19,20-epoxydocosapentaenoic acid (EDP), the major metabolites of ω-3 LCPUFAs generated by cytochrome P450, were key mediators of disease resolution [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Attenuation of choroidal neovascularization by dietary intake of ω-3 long-chain polyunsaturated fatty acids and lutein in mice

et al. 2018

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Dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and lutein each protect against age-related macular degeneration (AMD). We here examined the effects of ω-3 LCPUFAs and lutein supplementation in a mouse model of AMD. Mice were assigned to four groups: (1) a control group fed an ω-3 LCPUFA–free diet, (2) a lutein group fed an ω-3 LCPUFA–free diet with oral administration of lutein, (3) an ω-3 group fed an ω-3 LCPUFA–supplemented diet, and (4) an ω-3 + lutein group fed an ω-3 LCPUFA–supplemented diet with oral administration of lutein. Mice were fed the defined diets beginning 2 weeks before, and received lutein with an oral gavage needle beginning 1 week before, induction of choroidal neovascularization (CNV) by laser photocoagulation. The area of CNV measured in choroidal flat-mount preparations was significantly reduced in mice fed ω-3 LCPUFAs or lutein compared with those in the control group, and it was reduced in an additive manner in those receiving both ω-3 LCPUFAs and lutein. The concentrations of various inflammatory mediators in the retina or choroid were reduced in mice fed ω-3 LCPUFAs or lutein, but no additive effect was apparent. The generation of reactive oxygen species (ROS) in chorioretinal lesions revealed by dihydroethidium staining as well as the expression of NADPH oxidase 4 (Nox4) in the retina revealed by immunohistofluorescence and immunoblot analyses were attenuated by ω-3 LCPUFAs and lutein in a synergistic manner. Our results thus show that dietary intake of ω-3 LCPUFAs and lutein attenuated CNV in an additive manner and in association with suppression of inflammatory mediator production, ROS generation, and Nox4 expression. Dietary supplementation with both ω-3 LCPUFAs and lutein warrants further study as a means to protect against AMD.

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

Cited by 23 publications

References 30 publications

Differential Tissue Fatty Acids Profiling between Colorectal Cancer Patients with and without Synchronous Metastasis

Differential Tissue Fatty Acids Profiling between Colorectal Cancer Patients with and without Synchronous Metastasis

Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

Attenuation of choroidal neovascularization by dietary intake of ω-3 long-chain polyunsaturated fatty acids and lutein in mice

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