Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis

Vara-Messler, Marianela; Pasqualini, Marìa Eugenia; Comba, Andrea; Silva, Renata; Buccellati, Carola; Trenti, Annalisa; Trevisi, Lucia; Eynard, Aldo R.; Sala, Angelo; Bolego, Chiara; Valentich, Mirta A.

doi:10.1007/s00394-015-1096-6

Cited by 37 publications

(45 citation statements)

References 29 publications

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“…ALA is an essential omega3-PUFA, which is used to synthesize eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). ALA is associated with antitumorigenic effects in mice fed with an ALA-rich diet [46] and was reported to be toxic for MCF7 cells causing cell cycle arrest and apoptosis through mitochondrial membrane depolarization [47]. In MCF7 cells, it was shown that exogenously added ALA decreased growth via estrogen receptor-mediated signaling [48].…”

Section: Resultsmentioning

confidence: 99%

Lipid Profile and Aquaporin Expression under Oxidative Stress in Breast Cancer Cells of Different Malignancies

Rodrigues

Milković

Bujak

et al. 2019

Oxidative Medicine and Cellular Longevity

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Breast cancer is the major cause of tumor-associated mortality in women worldwide, with prognosis depending on the early discovery of the disease and on the type of breast cancer diagnosed. Among many factors, lipids could contribute to breast cancer malignancy by participating in cellular processes. Also, aquaporins are membrane channels found aberrantly expressed in cancer tissues that were correlated with tumor aggressiveness, progression, and metastasis. However, the differences in lipid profile and aquaporin expression between cell types of different malignant potential have never been investigated. Here, we selected three breast cancer cell lines representing the three major breast cancer types (hormone positive, HER2NEU positive, and triple negative) and analyzed their lipid profile and steady state lipid hydroperoxide levels to correlate with cell sensitivity to H2O2. Additionally, the expression profiles of AQP1, AQP3, and AQP5 and the Nrf2 transcription factor were evaluated, before and after oxidative challenge. We found that the lipid profile was dependent on the cell type, with the HER2-positive cells having the lowest level PUFA, whereas the triple negative showed the highest. However, in triple-negative cancer cells, a lower level of the Nrf2 may be responsible for a higher sensitivity to H2O2 challenge. Interestingly, HER2-positive cells showed the highest increase in intracellular ROS after oxidative challenge, concomitant with a significantly higher level of AQP1, AQP3, and AQP5 expression compared to the other cell types, with AQP3 always being the most expressed isoform. The AQP3 gene expression was stimulated by H2O2 treatment in hormone-positive and HER2NEU cells, together with Nrf2 expression, but was downregulated in triple-negative cells that showed instead upregulation of AQP1 and AQP5. The lipid profile and AQP gene expression after oxidative challenge of these particularly aggressive cell types may represent metabolic reprogramming of cancer cells and reflect a role in adaptation to stress and therapy resistance.

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Section: Resultsmentioning

confidence: 99%

Lipid Profile and Aquaporin Expression under Oxidative Stress in Breast Cancer Cells of Different Malignancies

Rodrigues

Milković

Bujak

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…It is the precursor to long chain ω-3 fatty acids and is found in vegetable and seed oils such as flax and walnuts, as well as in beans, legumes, grains, and leafy vegetables. In animal studies, it was shown that increased dietary levels of alpha-linoleic acid inhibit mammary tumor growth and metastasis (210).…”

Section: Phytonutrients Modulation Of Cox-2 Expressionmentioning

confidence: 99%

Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer

Desai

Prickril

Rasooly

2018

Nutrition and Cancer

171

110

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The link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways. Cyclooxygenase-2 (COX-2), a key enzyme in fatty acid metabolism, is upregulated during both inflammation and cancer. COX-2 is induced by pro-inflammatory cytokines at the site of inflammation and enhanced COX-2-induced synthesis of prostaglandins stimulates cancer cell proliferation, promotes angiogenesis, inhibits apoptosis, and increases metastatic potential. As a result, COX-2 inhibitors are a subject of intense research interest toward potential clinical applications. Epidemiological studies highlight the potential benefits of diets rich in phytonutrients for cancer prevention. Plants contain numerous phytonutrient secondary metabolites shown to modulate COX-2. Studies have shown that these metabolites, some of which are used in traditional medicine, can reduce inflammation and carcinogenesis. This review describes the molecular mechanisms by which phytonutrients modulate inflammation, including studies of carotenoids, phenolic compounds, and fatty acids targeting various inflammation-related molecules and pathways associated with cancer. Examples of pathways include those of COX-2, mitogen-activated protein kinase kinase kinase, mitogen-activated protein kinase, pro-inflammatory cytokines, and transcription factors like nuclear factor kappa B. Such phytonutrient modulation of COX-2 and inflammation continue to be explored for applications in the prevention and treatment of cancer.

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“…Ten days post inoculation, when tumor was palpable 52 and reached approximately a volume of 100 mm 3 , mice (n = 50) were randomly divided into 5 groups and different formulations were injected by the lateral tail vein, during a short period of isoflurane-induced inhalation anesthesia. All animals were followed for 10 weeks or until the end point was reached.…”

Section: Gm1-ptx Treatmentmentioning

confidence: 99%

“…BALB/c mice were injected intramuscularly in the right thigh with 0.1 mL of LMM3 cell suspension (1 × 10 6 cells in MEM without serum and antibiotics) to generate the primary tumor. After tumor induction, mice were housed until palpable tumor was detected (7 days) 52 . Animals with tumor developed were included for subsequent experiments.…”

mentioning

confidence: 99%

Monosialoganglioside GM1 reduces toxicity of Ptx and increase anti-metastasic effect in a murine mammary cancer model

Leonhard

Alasino

Pasqualini

et al. 2020

Sci Rep

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Having demonstrated the ability of monosialoganglioside GM1 micelles as oncology drug transporter, this work focuses on evaluating its application in an in vivo system, studying the toxicity and antitumoral effect of GM1-Ptx micellar formulation. The maximum tolerated dose (MTD) obtained after intravenous administration of GM1-Ptx in mice was 55 mg/kg and the 50% lethal dose (LD50) was 70 mg/kg. This value is higher than those described for the commercial formulations TAXOL and ABRAXANE, with LD50 of 30 and 45 mg/kg respectively. The antitumor activity, mortality and incidence of metastasis were studied on a murine model of mammary gland cancer. The GM1-Ptx formulation was administered i.v. at different doses for 9 weeks using empty GM1 micelles and saline as treatment controls. Once the treatments were completed, biochemical markers were quantified and histological tissue tests were performed. The most promising results were obtained with the treatment at a dose of 15 mg/kg/twice a week, condition in which a longer survival and significant reduction in the incidence of animals with metastasis, since only one 25% of the mice showed presence of pulmonary micro metastases.

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Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis

Abstract: These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention.

Cited by 37 publications

References 29 publications

Lipid Profile and Aquaporin Expression under Oxidative Stress in Breast Cancer Cells of Different Malignancies

Lipid Profile and Aquaporin Expression under Oxidative Stress in Breast Cancer Cells of Different Malignancies

Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer

Monosialoganglioside GM1 reduces toxicity of Ptx and increase anti-metastasic effect in a murine mammary cancer model

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