122 research outputs found
n–3 PUFA dietary supplementation inhibits proliferation and store-operated calcium influx in thymoma cells growing in Balb/c mice
The antitumor effect of daily individual administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2 g/kg body weight) in Balb/c mice bearing a transplantable thymoma was investigated. Mice received oleic acid (control group), EPA and DHA ethyl esters starting 10 days before tumor inoculation. Analysis of phospholipid composition of neoplastic cell revealed that EPA and DHA levels were significantly increased (63 and 22% increase) after EPA and DHA treatments, respectively. Conversely, decreased levels of arachidonic acid were found in both cases (19 and 24% decrease in EPA and DHA groups, respectively). EPA and DHA delayed the appearance of macroscopic ascites (100% of animal, from 7 to 28 days), prolonged animal survival (100% of animal, from 22 to 32 and 33 days, respectively) and reduced the percentage of proliferating tumor cells detected by immunostaining of proliferation cell nuclear antigen (PCNA) (80 and 85% decrease, respectively). Moreover, the regulatory effects of these dietary n–3 fatty acids on the influx of Ca2+, activated by depletion of intracellular stores with thapsigargin (Tg), were investigated. By using a Ca2+-free/Ca2+-reintroduction protocol and Fura-2 as fluorescent indicator of intracellular free Ca2+([Ca2+]i), we observed that EPA and DHA treatments markedly decreased Tg-induced rise in [Ca2+]i (49 and 37% decrease, respectively). This effect was related to the inhibition of the store-operated Ca2+ influx, as confirmed also by Mn2+ influx experiments. The inhibitory action of EPA and DHA on the store-operated Ca2+ influx could explain, at least in part, their antitumoral activity, as this Ca2+ mobilization pathway appears to be involved in the cell signaling occurring in non-excitable cells to evoke many cellular processes, including cell proliferation. —Calviello, G., P. Palozza, F. Di Nicuolo, N. Maggiano, and G. M. Bartoli. N–3 PUFA dietary supplementation inhibits proliferation and store-operated calcium influx in thymoma cells growing in Balb/c mice
N-3 polyunsaturated fatty acid effect in periodontal disease: state of art and possible mechanisms involved.
Anti-inflammatory properties have been widely reported for n-3 polyunsaturated fatty acids (PUFAs) and some studies have been focalized on their possible role in the modulation of gingivitis and alveolar bone resorption in periodontal disease (PD). Increased formation of arachidonic acid-derived inflammatory eicosanoids and augmented oxidative stress are two molecular mechanisms pathogenetically involved in the progression of PD and known to be inhibited by n-3 PUFAs in PD setting. The present review will focus also on other molecular pathways and factors known to be altered in the development of PD and known to be subject to n-3 PUFA modulation in other pathological settings different from PD. Overall, the available findings strongly encourage further experimental studies on animals subject to experimental PD and treated with n-3 PUFAs, long term n-3 PUFA intervention studies on PD patients and molecular studies to identify additional potential molecular routes of n-3 PUFA action in PD
Nanomedicine-based formulations containing \u3c9-3 polyunsaturated fatty acids: potential application in cardiovascular and neoplastic diseases.
Omega-3 polyunsaturated fatty acids (\u3c9-3 PUFAs) are dietary factors involved in the prevention of cardiovascular, inflammatory, and neoplastic diseases. A multidisciplinary approach - based on recent findings in nutritional science, lipid biochemistry, biotechnology, and biology of inflammation and cancer - has been recently employed to develop \u3c9-3 PUFA-containing nanoformulations with an aim to protect these fatty acids from degradation, increase their bioavailability and delivery to target tissues, and, thus, enhance their bioactivity. In some cases, these nanoformulations were designed to administer \u3c9-3 PUFAs in combination with other nutraceuticals or conventional/innovative drugs. The aim of this strategy was to increase the activities of the compounds contained in the nanoformulation and to reduce the adverse effects often induced by drugs. We herein analyze the results of papers evaluating the potential use of \u3c9-3 PUFA-containing nanomaterials in fighting cardiovascular diseases and cancer. Future directions in this field of research are also provide
Recent Advances in Nanotechnology for the Treatment of Melanoma.
Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies. In this regard, nanotechnology offers numerous benefits which could improve the life expectancy of melanoma patients with very low adverse effects. This review aims to examine the latest advances
in nanotechnology as an innovative strategy for treating melanoma. In particular, the use of different types of nanoparticles, such as vesicles, polymers, metal-based, carbon nanotubes, dendrimers, solid lipid, microneedles, and their combination with immunotherapies and vaccines will be discussed
Preparation and Study of Solid Lipid Nanoparticles Based on Curcumin, Resveratrol and Capsaicin Containing Linolenic Acid
Linolenic acid (LNA) is the most highly consumed polyunsaturated fatty acid found in the
human diet. It possesses anti-inflammatory effects and the ability to reverse skin-related disorders
related to its deficiency. The purpose of this work was to encapsulate LNA in solid lipid nanoparticles
(SLNs) based on curcumin, resveratrol and capsaicin for the treatment of atopic dermatitis. These
compounds were first esterified with oleic acid to obtain two moonoleate and one oleate ester, then
they were used for SLN matrix realization through the emulsification method. The intermediates of
the esterification reaction were characterized by FT-IR and 1N-MR analysis. SLNs were characterized
by dimensional analysis and encapsulation efficiency. Skin permeation studies, antioxidant and
anti-inflammatory activities were evaluated. LNA was released over 24 h from nanoparticles, and
resveratrol monooleate-filled SLNs exhibited a good antioxidant activity. The curcumin-based SLNs
loaded or not with LNA did not induce significant cytotoxicity in NCTC 2544 and THP-1 cells.
Moreover, these SLNs loaded with LNA inhibited the production of IL-6 in NCTC 2544 cells. Overall,
our data demonstrate that the synthesized SLNs could represent an efficacious way to deliver LNA to
skin cells and to preserve the anti-inflammatory properties of LNA for the topical adjuvant treatment
of atopic dermatiti
Anti-Irritant and Anti-Inflammatory Effects of DHA Encapsulated inResveratrol-Based Solid Lipid Nanoparticles in Human Keratinocytes.
We recently found that the dietary long chain omega-3 polyunsaturated fatty acid (LC-\u3c9-3 PUFA), docosahexaenoic acid (DHA), showed enhanced antineoplastic activity against colon cancer cells if encapsulated in resveratrol-based solid lipid nanoparticles (RV-SLNs). In the present study, we investigated whether the DHA enclosed in RV-SLNs (DHA-RV-SLNs) could have the potential of attenuating irritation and inflammation caused by environmental factors at the skin level. To this aim, we used two keratinocyte lines (HaCaT and NCTC 2544 cells) and exposed them to the cytotoxic action of the surfactant, sodium dodecyl sulfate (SDS), as an in vitro model of irritation, or to the pro-inflammatory activity of the cytokine TNF-\u3b1. We found that DHA enclosed in RV-SLNs significantly enhanced its ability to contrast the cytotoxic effect of SDS and to inhibit the SDS- and TNF-\u3b1-induced production of the inflammatory cytokines IL-1\u3b2, IL-6, and 1 MCP-1, in the two keratinocyte cell lines, as well as the NLRP3 inflammasome activation. Moreover, it more efficiently reduced the upsurge of reactive oxygen species (ROS) levels obtained in the presence of a pro-oxidant (H2O2). Overall, our findings suggest the possibility that a sustained dietary supplementation with DHA-RV-SLNs could efficiently protect skin from the pro-irritant and pro-inflammatory activity of environmental attacks
Omega-3 Polyunsaturated Fatty Acids: The Way Forward in Times of Mixed Evidence.
lmost forty years ago, it was first hypothesized that an increased dietary
intake of omega-3 polyunsaturated fatty acids (PUFA) from fish fat could exert
protective effects against several pathologies. Decades of intense preclinical
investigation have supported this hypothesis in a variety of model systems.
Several clinical cardiovascular studies demonstrated the beneficial health
effects of omega-3 PUFA, leading medical institutions worldwide to publish
recommendations for their increased intake. However, particularly in recent
years, contradictory results have been obtained in human studies focusing on
cardiovascular disease and the clinical evidence in other diseases, particularly
chronic inflammatory and neoplastic diseases, was never established to a degree
that led to clear approval of treatment with omega-3 PUFA. Recent data not in
line with the previous findings have sparked a debate on the health efficacy of
omega-3 PUFA and the usefulness of increasing their intake for the prevention of
a number of pathologies. In this review, we aim to examine the controversies on
the possible use of these fatty acids as preventive/curative tools against the
development of cardiovascular, metabolic, and inflammatory diseases, as well as
several kinds of cancer
Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain n-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs
A potential complementary role of the dietary long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFA) in combination with innovative mono-targeted therapies has recently been proposed. These compounds are thought to act pleiotropically to prevent the development and progression of a variety of cancers, including breast cancer. We hereinafter critically analyze the reports investigating the ability of LCn-3 PUFA to modulate the Ras/ERK and the phosphoinositide survival signaling pathways often aberrantly activated in breast cancer and representing the main targets of innovative therapies. The in vitro or in vivo animal and human interventional studies published up to January 2017 investigating the effects of LCn-3 PUFA on these pathways in normal and cancerous breast cells or tissues were identified through a systematic search of literature in the PubMed database. We found that, in most cases, both the in vitro and in vivo studies demonstrated the ability of LCn-3 PUFA to inhibit the activation of these pro-survival pathways. Altogether, the analyzed results strongly suggest a potential role of LCn-3 PUFA as complementary agents in combination with mono-targeted therapies. Moreover, the results indicate the need for further in vitro and human interventional studies designed to unequivocally prove the potential adjuvant role of these fatty acids
ROS-Responsive PLGA-NPs for Co-Delivery of DTX and DHA for Colon Cancer Treatment
The aim of this work was to evaluate the antineoplastic effect of newly synthesized
nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) alone or PLGA esterified with 2,2′-
[propane-2,2-diylbis (thio)] diacetic acid (TKL), loaded with docetaxel (DTX) and/or docosahexaenoic
acid (DHA), as innovative site-specific therapeutic carriers. The obtained materials were characterized
by FT-IR and 1H-NMR, while the dimensional analysis of the nanoparticles obtained was performed
by Dynamic Light Scattering. The encapsulation efficiency of the nanoparticles was evaluated, and
in vitro skin permeation tests were also performed. The antitumor activity of the nanomaterial was
studied in the human adenocarcinoma HCT116 cell line. In particular, viability tests in bidimensional
culture, as well as in tumor spheroids, were conducted. The use of these nanocarriers could facilitate
the stable and efficient delivery of DTX and DHA through the upper segments of the gastrointestinal
tract to the colon. In addition, the presence of the ROS-sensitive 2,2′-[propane-2,2-diylbis (thio)]
diacetic acid in their matrix should promote the site-specific release of DTX in the tumor mass, where
high levels of reactive oxygen species could be found
Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain n-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs
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