Romina Molinari

Dietary ω-3 Polyunsaturated Fatty Acid DHA: A Potential Adjuvant in the Treatment of Cancer

ω-3 Polyunsaturated fatty acids (PUFAs), mainly present in fish oil, are part of the human diet. Among PUFAs, docosahexaenoic acid (DHA) has received particular attention for its anti-inflammatory, antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties. These data suggest that DHA can exert antitumor activity potentially representing an effective adjuvant in cancer chemotherapy. This review is focused on current knowledge supporting the potential use of DHA for the enhancement of the efficacy of anticancer treatments in relation to its ability to enhance the uptake of anticancer drugs, regulate the oxidative status of tumor cells, and inhibit tumor cell invasion and metastasis.

Docosahexaenoic acid induces apoptosis in the human PaCa-44 pancreatic cancer cell line by active reduced glutathione extrusion and lipid peroxidation.

Abstract: We investigated the ability of fatty acids to induce growth inhibition and apoptosis in the human PaCa-44 pancreatic cancer cell line and the mechanism(s) underlying apoptosis. Butyric acid, α-linoleic acid, and docosahexaenoic acid (DHA) were supplemented at 200 μM concentration in the medium of cell cultures. Our results showed that all fatty acids inhibited cell growth, whereas only DHA induced cell apoptosis. An oxidative process was implicated in apoptosis induced by DHA because butylated hydroxytoluene and vitamin E prevented lipid peroxidation and reversed apoptosis. Intracellular and extracellular glutathione [reduced glutathione (GSH) and oxidized glutathione (GSSG)] concentrations were measured following DHA treatment in the presence or in the absence of GSH extrusion inhibitors such as cystathionine or methionine. DHA induced intracellular GSH depletion without affecting intracellular GSSG concentration and increased extracellular GSH and GSSG levels. Intracellular GSH depletion and extracellular GSH increase were both reversed by cystathionine. Inhibition of active GSH extrusion from the cell by cystathionine or methionine completely reversed lipid peroxidation and apoptosis. These data document the antiproliferative and apoptotic activities of DHA. The date provide evidence that intracellular GSH depletion represents an active extrusion process rather than a consequence of an oxidative stress, suggesting a causative role of GSH depletion in DHA-induced apoptosis.

Development of gluten-free bread using tartary buckwheat and chia flour rich in flavonoids and omega-3 fatty acids as ingredients

In this study, chia seed flour, which is rich in omega-3 alpha-linolenic acid, and common and tartary buckwheat flour, which has a high antioxidant activity, were integrated into different types of bread with the aim of improving their nutritional value and healthy features. Our results indicate that bread made with chia and tartary buckwheat flour was more acceptable in many nutritional aspects compared to the control (common wheat bread); it contained a higher amount of protein (20%), insoluble dietary fibres (74%), ash (51%), and alpha-linolenic acid (67.4%). Moreover, this bread possessed lower energy (14%) and carbohydrate contents (24%) compared to the control. Tartary buckwheat also improved the total antioxidant capacity of the bread (about 75%) and provided a considerable amount of flavonoids, which are healthy non-nutritional compounds. Overall, chia and tartary buckwheat represent excellent raw materials for the formulation of gluten-free bread with high nutritional value.

Synthesis of a novel ester of hydroxytyrosol and α-lipoic acid exhibiting an antiproliferative effect on human colon cancer HT-29 cells

A novel ester of hydroxytyrosol and α-lipoic acid was synthesized in satisfactory yield by original and simple procedures and evaluated about its antiproliferative activity on the human colorectal adenocarcinoma HT-29 cell line. The compound exhibited a cell growth inhibitory activity significantly more potent than the corresponding parent natural compounds, very likely due to the induction of cell cycle arrest in the G2/M phase. These data suggest that the novel ester might exert a more effective antitumour activity than hydroxytyrosol and α-lipoic acid.

Induction of Apoptosis in Human Pancreatic Cancer Cells by Docosahexaenoic Acid

Abstract: Polyunsaturated fatty acids have been indicated to induce anti‐proliferative and/or apoptotic effects in various tumor cells. We showed that, at a 200‐μM concentration, both alpha‐linoleic (18:2 n‐6; LA) or docosahexaenoic (22:6 n‐3; DHA) acid inhibited cell growth, while only DHA induced apoptosis in the human Paca‐44 pancreatic cancer cell line. Investigating the mechanism underlying DHA‐induced apoptosis, we showed that DHA induced a rapid and dramatic (>60%) intracellular depletion of reduced glutathione (GSH), without affecting oxidized glutathione (GSSG). Moreover, using two specific inhibitors of carrier‐mediated GSH extrusion, cystathionine or methionine, we observed that GSH depletion occurred via an active GSH extrusion, and that inhibition of GSH efflux completely reversed apoptosis. These results provide the first evidence for a possible causative role of GSH depletion in DHA‐induced apoptosis.

Impact of Omega-3 Fatty Acids on the Gut Microbiota

Long-term dietary habits play a crucial role in creating a host-specific gut microbiota community in humans. Despite the many publications about the effects of carbohydrates (prebiotic fibers), the impact of dietary fats, such as omega-3 polyunsaturated fatty acids (PUFAs), on the gut microbiota is less well defined. The few studies completed in adults showed some common changes in the gut microbiota after omega-3 PUFA supplementation. In particular, a decrease in Faecalibacterium, often associated with an increase in the Bacteroidetes and butyrate-producing bacteria belonging to the Lachnospiraceae family, has been observed. Coincidentally, a dysbiosis of these taxa is found in patients with inflammatory bowel disease. Omega-3 PUFAs can exert a positive action by reverting the microbiota composition in these diseases, and increase the production of anti-inflammatory compounds, like short-chain fatty acids. In addition, accumulating evidence in animal model studies indicates that the interplay between gut microbiota, omega-3 fatty acids, and immunity helps to maintain the intestinal wall integrity and interacts with host immune cells. Finally, human and animal studies have highlighted the ability of omega-3 PUFAs to influence the gut–brain axis, acting through gut microbiota composition. From these findings, the importance of the omega-3 connection to the microbiota emerges, encouraging further studies.

Effect of Dietary ω-3 Polyunsaturated Fatty Acid DHA on Glycolytic Enzymes and Warburg Phenotypes in Cancer

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of lipids that has been shown to have beneficial effects on some chronic degenerative diseases such as cardiovascular diseases, rheumatoid arthritis, inflammatory disorders, diabetes, and cancer. Among ω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) has received particular attention for its antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties, even though the involved molecular mechanisms are not well understood. Recently, some in vitro studies showed that DHA promotes the inhibition of glycolytic enzymes and the Warburg phenotype. For example, it was shown that in breast cancer cell lines the modulation of bioenergetic functions is due to the capacity of DHA to activate the AMPK signalling and negatively regulate the HIF-1α functions. Taking into account these considerations, this review is focused on current knowledge concerning the role of DHA in interfering with cancer cell metabolism; this could be considered a further mechanism by which DHA inhibits cancer cell survival and progression.

Diets rich in whole wheat improve redox status and enhance immune responses in rats

Abstract Whole wheat and refined wheat differ substantially for dietary fibre and polyphenol contents, however, the exact relationship between the in vitro contents and in vivo functions have not been well established. Two groups of growing rats were fed for 6 weeks with diets containing 53% of whole durum and refined durum wheat flours. In plasma and in mesenteric lymphocytes parameters of redox status and in lymphocytes the rate of cell proliferation and the type of immune response were measured. Plasma antioxidant activity showed that whole wheat was able to increase antioxidative status with respect to refined wheat and to reduce the carbonyl content. The diets rich in whole wheat can improve proliferative responses with respect to refined wheat. The results indicated that a constant intake of whole wheat may have important implications for health, by acting as modulator of immune function and redox status.

Risk assessment of population exposure to toxic trace elements via consumption of vegetables and fruits grown in some mining areas of Armenia

ABSTRACT Consumption of unsafe food is one of the most important public health concerns. Trace elements’ contamination caused by direct or indirect activities of mining industries is of importance in this respect. The present study was conducted to assess the chronic dietary exposure and related health risks of trace elements through the intake of selected vegetables and fruits grown under the impact of mining industry in Syunik region (Armenia). Consumption data were obtained via food frequency questionnaire and the concentrations of Cu, Mo, Ni, Cr, Pb, Zn, Hg, and Cd in different fruits and vegetables were determined. Moreover, by combining concentration data with consumption data, estimated daily intake, and target hazard quotient were assessed for each element. The results obtained showed that mean concentrations for Pb and Hg in some vegetables exceeded maximum acceptable levels set by international organizations. Hazard indexes > 1 have been obtained in some cases indicating that for some vegetables (particularly for potato, carrot, maize, onion leaf, grape, bean, beet, sweet pepper, eggplant, and tomato) habitual consumption has a potential to pose adverse health effect to the local population.

Pasta containing tartary buckwheat sprouts prevents DNA damage in spontaneously hypertensive rats

Abstract Recent studies have shown that DNA damage occurs more often in hypertensive patients than non-hypertensive individuals. Here, we analyzed the in vivo effect of pasta containing 30% of tartary buckwheat sprouts (TBSP) on spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKY) to elucidate if TBSP could have an anti-genotoxic effect in hypertensive animal models. Both SHRs and WKY rats were divided into two groups and fed for six weeks with 5 g of TBSP and durum wheat flour commercial pasta, respectively. Our results showed that a diet rich in TBSP has anti-genotoxic effect. Indeed, SHRs fed with TBSP exhibited a significant decrease in DNA damage (38%) and more efficient DNA repair (84%) compared to SHRs fed with commercial pasta.