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

A novel hydroxytyrosol-lipoic acid derivative has been synthesized. Key steps are an esterification reaction between tyrosol and cJipoic acid derivatives and a regioselective aromatic hydroxylation ofthe monohydroxylated ester performed by 2-iodoxybenzoic acid (IBX) followed by an in situ reductionw ith sodium dithionite (Na2S2O4T).h e novel estere xhibited an antiproliferative effect on the human colorectal adenocarcinoma HT-29 cell line signifrcantly more potent than its parent compounds

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

The omega-3 polyunsaturated fatty acids ( -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 -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-1 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

Boron Neutron Capture Therapy (BNCT) in an oral precancer model: Therapeutic benefits and potential toxicity of a double application of BNCT with a six-week interval

Given the clinical relevance of locoregional recurrences in head and neck cancer, we developed a novel experimental model of premalignant tissue in the hamster cheek pouch for long-term studies and demonstrated the partial inhibitory effect of a single application of Boron Neutron Capture Therapy (BNCT) on tumor development from premalignant tissue. The aim of the present study was to evaluate the effect of a double application of BNCT with a 6 week interval in terms of inhibitory effect on tumor development, toxicity and DNA synthesis. We performed a double application, 6 weeks apart, of (1) BNCT mediated by boronophenylalanine (BPA-BNCT); (2) BNCT mediated by the combined application of decahydrodecaborate (GB-10) and BPA [(GB-10 + BPA)-BNCT] or (3) beam-only, at RA-3 nuclear reactor and followed the animals for 8 months. The control group was cancerized and sham-irradiated. BPA-BNCT, (GB-10 + BPA)-BNCT and beam-only induced a reduction in tumor development from premalignant tissue that persisted until 8, 3, and 2 months respectively. An early maximum inhibition of 100% was observed for all 3 protocols. No normal tissue radiotoxicity was detected. Reversible mucositis was observed in premalignant tissue, peaking at 1 week and resolving by the third week after each irradiation. Mucositis after the second application was not exacerbated by the first application. DNA synthesis was significantly reduced in premalignant tissue 8 months post-BNCT. A double application of BPA-BNCT and (GB-10 + BPA)-BNCT, 6 weeks apart, could be used therapeutically at no additional cost in terms of radiotoxicity in normal and dose-limiting tissues.Fil: Monti Hughes, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Comision Nacional de Energia Atomica. Gerencia D/area de Energia Nuclear. Gerencia de Ingenieria Nuclear (cab). Departamento de Reactores de Investigacion.; ArgentinaFil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Thorp, Silvia Inés. Comision Nacional de Energia Atomica. Gerencia de Area Carem. Departamento de Instrumentacion y Cableado (cab).; ArgentinaFil: Miller, Marcelo. Comision Nacional de Energia Atomica. Gerencia de Area Carem. Departamento de Instrumentacion y Cableado (cab).; ArgentinaFil: Itoiz, María Elina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Aromando, Romina F.. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Molinari, Ana Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Nigg, David W.. Idaho National Laboratory; Estados UnidosFil: Trivillin, Verónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; ArgentinaFil: Schwint, Amanda Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentin

"Sequential" boron neutron capture therapy (BNCT): A novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model

In the present study the therapeutic effect and potential toxicity of the novel "“Sequential"†boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential"BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential"BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ±2% and 91 ±3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ±5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ±12% and 60 ±22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential"BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue.Fil: Molinari, Ana Julia. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; ArgentinaFil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica; ArgentinaFil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica; ArgentinaFil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; ArgentinaFil: Miller, Marcelo. Comisión Nacional de Energía Atómica; ArgentinaFil: Itoiz, María Elina. Universidad de Buenos Aires; Argentina. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aromando, Romina F.. Universidad de Buenos Aires; ArgentinaFil: Nigg, David W.. Idaho National Laboratory; Estados UnidosFil: Quintana, Jorge. Comisión Nacional de Energía Atómica; ArgentinaFil: Santa Cruz, Gustavo Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Retinoic Acids in the Treatment of Most Lethal Solid Cancers

Although the use of oral administration of pharmacological all-trans retinoic acid (ATRA) concentration in acute promyelocytic leukaemia (APL) patients was approved for over 20 years and used as standard therapy still to date, the same use in solid cancers is still controversial. In the present review the literature about the top five lethal solid cancers (lung, stomach, liver, breast, and colon cancer), as defined by The Global Cancer Observatory of World Health Organization, and retinoic acids (ATRA, 9-cis retinoic acid, and 13-cis retinoic acid, RA) was compared. The action of retinoic acids in inhibiting the cell proliferation was found in several cell pathways and compartments: from membrane and cytoplasmic signaling, to metabolic enzymes, to gene expression. However, in parallel in the most aggressive phenotypes several escape routes have evolved conferring retinoic acids-resistance. The comparison between different solid cancer types pointed out that for some cancer types several information are still lacking. Moreover, even though some pathways and escape routes are the same between the cancer types, sometimes they can differently respond to retinoic acid therapy, so that generalization cannot be made. Further studies on molecular pathways are needed to perform combinatorial trials that allow overcoming retinoic acids resistance

The Seed of Industrial Hemp (Cannabis sativa L.): Nutritional Quality and Potential Functionality for Human Health and Nutrition

Hempseeds, the edible fruits of the Cannabis sativa L. plant, were initially considered a by-product of the hemp technical fibre industry. Nowadays, following the restorationing of the cultivation of C. sativa L. plants containing an amount of delta-9-tetrahydrocannabinol (THC) <0.3% or 0.2% (industrial hemp) there is a growing interest for the hempseeds production due to their high nutritional value and functional features. The goal of this review is to examine the scientific literature concerning the nutritional and functional properties of hempseeds. Furthermore, we revised the scientific literature regarding the potential use of hempseeds and their derivatives as a dietary supplement for the prevention and treatment of inflammatory and chronic-degenerative diseases on animal models and humans too. In the first part of the work, we provide information regarding the genetic, biochemical, and legislative aspects of this plant that are, in our opinion essential to understand the difference between “industrial” and “drug-type” hemp. In the final part of the review, the employment of hempseeds by the food industry as livestock feed supplement and as ingredient to enrich or fortify daily foods has also revised. Overall, this review intends to encourage further and comprehensive investigations about the adoption of hempseeds in the functional foods field

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