A potential role of PUFAs and COXIBs in cancer chemoprevention

Polyunsaturated fatty acids (PUFAs), particularly the \u3c9-3 PUFAs and COXIBs have been associated with decreased inflammation and the prevention of tumorigenesis. \u3c9-3 PUFAs have shown to display multiple antitumour actions, while \u3c9-6 PUFAs and its derived eicosanoids promote the effects in cancer cell growth, angiogenesis, and invasion. \u3c9-3 PUFAs may act by suppressing the metabolism of arachidonic acid to form proinflammatory mediators or as a precursors of novel lipid mediators with pro-resolving activity, while COXIBs are able to modulate inflammatory response by inhibiting cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase overexpressed in several human cancers. As recently has been postulated, the anti-inflammation and pro-resolution processes are not equivalent. A family of lipid mediators from \u3c9-3 PUFAs can act as agonist promoting resolution, while antinflammatory agents such as COXIBs may act as antagonists limiting the inflammatory response. The present paper reviews the current knowledge about the role of PUFAs and its derivatives (metabolites), as well as the COXIBs activity in cancer process as a sinergic therapeutic alternative for cancer treatment

Effect of essential fatty acids on cell survival in an in-vitro model of breast cancer

Chirostoma jordani is a native annual species inhabiting lacustrine waters of the Central Mexico Plateau. It is widely distributed and is currently facing high environmental pressures. Five experiments were performed to study the reproductive performance of this species. Four of the experiments were conducted in 270-L indoor recirculation tanks. Two males and one female at the first stage of reproduction were included in each test. A photoperiod of 14 light hours and 10 dark hours was used. In a fifth experiment, 10 females and 15 males were kept in an outdoor 3,000-L recirculation tank under natural photoperiod. The number of spawns, fertilised eggs and 30-day-old juveniles were counted and the survival rate was calculated. The results indicated significant differences (P<0.05) between treatments. Higher spawn numbers and greater egg production were observed under controlled photoperiod, and higher numbers of juveniles and a higher survival rate were observed under natural photoperiod. The trials exhibited different patterns of egg production during the experiment. The egg production in the natural-photoperiod trials followed a polynomial curve model. In contrast, the trials under the controlled photoperiod showed an irregular pattern of increases and decreases in egg production

Effects of \u3c9-3 PUFA-enriched diet on growth parameters in a syngenic murine model of breast adenocarcinoma: a possible role for estrogen receptor alpha

ackground: Breast cancer (BC) is the most common tumour among women and 75% of BC are estrogen receptor (ER)-dependent. In particular, ER\u3b1 promotes tumour growth, while ER\u3b2 has an anti-proliferative effect [1]. Epidemiological data have linked \u3c9-3 polyunsaturated fatty acid (PUFA) consumption to lower incidence of BC and several experimental studies showed the anti-proliferative effects of \u3c9-3 fish oil in different tumour models [2,3]. Chia seed oil is rich in \u3b1-linolenic acid (ALA 18:3 \u3c9-3), while corn oil is rich in linoleic acid (LA 18:2 \u3c9-6), precursors of eicosapentaenoic acid (EPA) and arachidonic acid (AA), respectively. Based on substrate availability, these FAs give rise to different eicosanoid signatures with opposite effects in cancer [4]. \u3c9-3 PUFAs generate both anti-inflammatory prostanoids and reactive oxygen species (ROS), which in turn could affect NF-\u3baB. Indeed, NF-\u3baB belongs to a family of transcription factors with a key role in inflammation and oxidative stress, but its role in tumour development is still controversial [5]. The aim of the study was to determine possible processes that are activated by dietary lipids regulating BC growth and metastasis. Methods: 40 BALB/c mice were divided in 2 groups and fed 1) an experimental diet enriched with Chia Oil (ChO) as a source of \u3c9-3, or 2) a control diet with Corn Oil (CO) as a source of \u3c9-6. Afterwards, mice were inoculated with mouse BC cells (LM3) and tumour parameters were recorded after 35 days. FA incorporation into cell membranes was analyzed by gas chromatography, whereas eicosanoid production was evaluated by HPLC. Mitotic or apoptotic figures were assessed in haematoxylin/eosin-stained tumour sections. Western blotting for p-I\u3baB\u3b1/I\u3baB\u3b1, as an index of NF-\u3baB activation, and ER\u3b1/ER\u3b2 was performed in tumour lysates. ROS release was evaluated in LM3 cells after treatment with either AA or DHA by flow cytometry in the presence of DCFHDA. Results: Tumour incidence was higher in CO-fed mice (100%) compared with ChO-fed mice (85%). Tumour weight (1.0\ub10.2 vs 2.2\ub10.2 g, p<0.05) and volume (4.4\ub10.4 vs 7.2\ub11.0 mm, p<0.05) as well as metastasis number (7.4\ub10.8 vs 10.0\ub10.1, p<0.05) were lower, whereas tumour latency time (22\ub11 vs 15\ub12 d, p<0.05) was higher in ChO-fed mice. Accordingly, a lower number of mitosis and a higher number of apoptotic figures were recorded in tumours from ChO- compared with CO-fed mice. Cell membranes of tumours from ChO-fed mice showed a higher percentage of \u3c9-3 PUFAs compared with those from CO-fed mice and generated lower amounts of \u3c9-6 pro-inflammatory eicosanoids 13-HODE (25.1\ub12.8 vs 43.1\ub14.8 ng/107cells, p<0.05), 15-HETE (13.2\ub10.8 vs 86.8\ub15.4 ng/107cells, p<0.05) and 5-HETE (11.0\ub10.7 vs 95.7\ub16.9 ng/107cells, p<0.05). Unexpectedly, the p-I\u3baB\u3b1/I\u3baB\u3b1 ratio was higher in tumor lysates from ChO group. Consistently, ROS production was higher in tumor cells challenged with \u3c9-3 with respect to \u3c9-6 PUFAs. Finally, ER\u3b1 amount was down-regulated by \u3c9-3 PUFAs (-65%, p<0.005) in tumor lysates, while ER\u3b2 was unaffected. Conclusion: \u3c9-3 PUFA incorporation into cell membranes shifted lipid mediator profile toward an anti-inflammatory, anti-tumour effect. In addition, \u3c9-3 PUFAs produced higher ROS amounts with respect to \u3c9-6 PUFAs in vitro, consistent with increased NF-\u3baB activation in vivo. Finally, the \u3c9-3 PUFA-enriched diet profoundly down-regulated ER\u3b1 without affecting ER\u3b2 expression. Overall, these data support a potential role for dietary \u3c9-3 PUFAs in BC treatment in association with antiestrogens. References 1. Chen GG et al. Med Res Rev. 2008;28(6):954-74 2. Berquin IM et al. Cancer Lett. 2008;269(2):363-77. 3. Vara Messler M et al. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2012; 30(2):174-87. 4. Zhang G et al. Proc Natl Acad Sci U S A. 2013;110(16):6530-35. 5. Ben-Neriah Y et al. Nat Immunol. 2011;12(8):715-23

Increased dietary levels of &#945;-linoleic acid inhibit mammary tumor growth and metastasis

Objective: The aim of this study was to determine whether \u3b1-linolenic acid (ALA \u3c9-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma. Materials and methods: BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA \u3c9-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma. Results: After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from \u3c9-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) \u3b1 expression, a recognized breast cancer promotor while showing an opposite effect on ER\u3b2 in tumor lysates. Conclusion: These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention