Asparaginase Treatment of Sea Buckthorn Berries as an Effective Tool for Acrylamide Reduction in Nutritionally Enriched Wholegrain Wheat, Rye and Triticale Biscuits.

Sea buckthorn pomace is a by-product of juice production, which is still rich in bioactive compounds. After drying, the pomace can be effectively used as a valuable addition to bakery products supporting their nutritional value. However, due to the high content of the amino acid asparagine in sea buckthorn, this promising material contributes to the undesirable formation of acrylamide. To reduce the risk from this potentially carcinogenic compound, enzymatic treatment of sea buckthorn with asparaginase was applied, which resulted in a substantial reduction of asparagine content from 1834 mg/kg in untreated dried sea buckthorn pomace to 89 mg/kg in enzymatically treated dried sea buckthorn pomace. 10% substitution of wholegrain cereal flour with enzymatically treated sea buckthorn pomace powder in rye and triticale biscuits resulted in a 35% reduction in acrylamide content, in the case of wholegrain wheat biscuits up to a 64% reduction, compared to biscuits with untreated sea buckthorn pomace powder. This study confirmed that treating fruit with asparaginase is an effective way to reduce health risk caused by acrylamide in biscuits enriched with nutritionally valuable fruit pomace.

Acrylamide and 5-hydroxymethylfurfural in thermally treated non-wheat flours and respective breads.

This is the first report about the influence of dry and wet heat treatment on acrylamide content in flours and, subsequently, in breads. It was shown that during production of some breads acrylamide content decreases. Dry heating of non-wheat flour resulted in acrylamide in flours of sorghum (160 µg/kg); millet (447 µg/kg); barley (516 µg/kg); triticale (868 µg/kg); rye (1833 µg/kg); oat (1951 µg/kg). Hydrothermal heating had a negligible impact on acrylamide formation. In breads made from flour blends consisted of 70% of dry thermally and 30% of hydrothermally treated flours of millet, sorghum, oat, and rye, respectively, acrylamide was detected in the range from 105 to 312 µg/kg. 5-hydroxymethylfurfural probably contributing to acrylamide formation in bread was detected in the range from 2.0 mg/kg to 44.3 mg/kg in dry heated flours; in hydrothermally treated flours was below LOQ (1.7 mg/kg); in breads was between 3.3 and 8.0 mg/kg.

Inhibition of Glycolysis Suppresses Cell Proliferation and Tumor Progression In Vivo: Perspectives for Chronotherapy.

A high rate of glycolysis is considered a hallmark of tumor progression and is caused by overexpression of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Therefore, we analyzed the possibility of inhibiting tumor and endothelial cell metabolism through the inhibition of PFKFB3 by a small molecule, (E)-1-(pyridin-4-yl)-3-(quinolin-2-yl)prop-2-en-1-one (PFK15), as a promising therapy. The effects of PFK15 on cell proliferation and apoptosis were analyzed on human umbilical vein endothelial cells (HUVEC) and the human colorectal adenocarcinoma cell line DLD1 through cytotoxicity and proliferation assays, flow cytometry, and western blotting. The results showed that PFK15 inhibited the proliferation of both cell types and induced apoptosis with decreasing the Bcl-2/Bax ratio. On the basis of the results obtained from in vitro experiments, we performed a study on immunodeficient mice implanted with DLD1 cells. We found a reduced tumor mass after morning PFK15 treatment but not after evening treatment, suggesting circadian control of underlying processes. The reduction in tumor size was related to decreased expression of Ki-67, a marker of cell proliferation. We conclude that inhibition of glycolysis can represent a promising therapeutic strategy for cancer treatment and its efficiency is circadian dependent.

Synergic effects of inhibition of glycolysis and multikinase receptor signalling on proliferation and migration of endothelial cells.

Activated endothelial cells play a crucial role in the formation of new blood vessels, a process known as angiogenesis, which can underlie the development of several diseases. Different antiangiogenic therapies aimed against vascular endothelial growth factor (VEGF), the dominant pro-angiogenic cytokine, have been developed. Because the treatment is limited in its efficiency and has side effects, new approaches are currently being evaluated. One of them is aimed at blocking glycolysis, the dominant energetic pathway of activated endothelial cells during vessel sprouting. In the present study we investigated the efficiency of a combined strategy to inhibit glycolysis and block VEGF action on proliferation and migration in human endothelial cells. Human endothelial cells (HUVECs) were treated with different doses of the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) in combination with the multikinase inhibitor sunitinib l-malate. Our results show that HUVECs with reduced glycolytic activity are more sensitive to co-administered sunitinib. Analysis of post-receptor pathways controlling proliferation and migration of HUVECs showed suppression of phosphorylated PI3K/Akt and ERK1/2 after exposure to sunitinib but not to 3PO in 10 µM concentration. Our results suggest that simultaneous inhibition of energy metabolism and blocking of pro-angiogenic growth factor signalling pathways can be a promising strategy to inhibit the pathological form of angiogenesis.