Assessment of Heparanase-Mediated Angiogenesis Using Microvascular Endothelial Cells: Identification of λ-Carrageenan Derivative as a Potent Anti Angiogenic Agent.

Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent heparanase inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective heparanase inhibitor with an IC of 7.

Production of heparin and λ-carrageenan anti-heparanase derivatives using a combination of physicochemical depolymerization and glycol splitting.

Strongly associated with tumor angiogenesis and metastasis, the enzyme heparanase is an endo-β-d-glucuronidase which is overexpressed in the tumor microenvironment. Its inhibition could be one of the most promising anti-angiogenic approaches to date. Although heparin is known as a good heparanase inhibitor, it also possesses major anticoagulant properties that may be incompatible with its use as an anti-angiogenic agent, hence the considerable interest for other sources of sulfated polysaccharides.

Identification of ace inhibitory cryptides in Tilapia protein hydrolysate by UPLC-MS/MS coupled to database analysis.

An ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry method was developed and applied to identify short angiotensin-I-converting enzyme (ACE) inhibitory cryptides in Tilapia (Oreochromis Niloticus) protein hydrolyzate. A database was created with previously identified ACE-inhibitory di- and tripeptides and the lowest molecular weight fraction of Tilapia hydrolysate was analysed for coincidences. Only VW and VY were identified.

Alteration of cathepsin D trafficking induced by hypoxia and extracellular acidification in MCF-7 breast cancer cells.

The microenvironment that surrounds tumor cells is characterized by hypoxic conditions and extracellular acidity. These hostile conditions induce crucial changes in cell behavior and can promote the secretion of many soluble factors such as growth factors, cytokines and enzymes. The lysosomal aspartyl-endopeptidase cathepsin D (CD) is a marker of poor prognosis in breast cancer and is associated with a metastatic risk.

Anti-heparanase activity of ultra-low-molecular-weight heparin produced by physicochemical depolymerization.

Heparanase is an endo-β-D-glucuronidase that plays an important role in cancer progression, in particular during tumor angiogenesis and metastasis. Inhibiting this enzyme is considered as one of the most promising approaches in cancer therapy. Heparin is a complex glycoaminoglycan known as a strong inhibitor of heparanase.

Measuring angiotensin-I converting enzyme inhibitory activity by micro plate assays: comparison using marine cryptides and tentative threshold determinations with captopril and losartan.

To determine the angiotensin-I converting enzyme (ACE) inhibitory activity of marine cryptides, different methods were tested. ACE inhibition was measured using two synthetic substrates, (N-[3-(2-furyl) acryloyl]-Phe-Gly-Gly (FAPGG) and N-hippuryl-His-Leu hydrate salt (HHL)), and a natural one, angiotensin-I. The IC50 value (defined as the concentration of inhibitory molecule needed to inhibit 50% of the ACE activity) of the reference synthetic inhibitor captopril was in the nanomolar range (1.

Ultrasonic-assisted preparation of a low molecular weight heparin (LMWH) with anticoagulant activity.

Low molecular weight heparin (LMWH) is currently used as an anticoagulant agent and constitutes an alternative to unfractionated heparin, which is the cause of serious adverse drug reaction such as heparin-induced thrombocytopenia (HIT). Commercially available LMWH is produced by enzymatic depolymerization that is costly or by chemical methods that are generally carried out under conditions that could imply side reactions that reduce final product efficiency and yields. In this work, we present the use of a physicochemical method for the production of LMWH.

Cathepsin D activity and selectivity in the acidic conditions of a tumor microenvironment: Utilization in the development of a novel Cathepsin D substrate for simultaneous cancer diagnosis and therapy.

Pro-Cathepsin D (pCD) is an aspartyl endopeptidase which is over expressed in many cancers. This over expression generally led to its secretion into the extracellular culture medium of cancer cells. Moreover, pCD can auto activate and cleave its substrates at an acidic pH compatible with that found in tumor microenvironments (TME).

Goat whey fermentation by Kluyveromyces marxianus and Lactobacillus rhamnosus release tryptophan and tryptophan-lactokinin from a cryptic zone of alpha-lactalbumin.

Angiotensin-I-Converting Enzyme (ACE) inhibitors peptides were produced from unsupplemented acid goat whey fermented aerobically for 168 h by Kluyveromyces marxianus and Lactobacillus rhamnosus. This yeast-lactobacillus association is GRAS. Two novel lactokinins were identified: NYW and W with IC50 of 20 and 0.

Peptides released from acid goat whey by a yeast-lactobacillus association isolated from cheese microflora.

Seven lactobacilli and a variety of microflora extracted from twenty five commercial cheeses were grown on unsupplemented acid goat whey and screened for their capacity to hydrolyse whey proteins [alpha-lactalbumin (alpha-la) and beta-lactoglobulin (beta-lg)] and to generate peptides. Fermentations were performed aerobically or anaerobically at 37 degrees C using crude or pre-heated whey (10 min at 65, 75 or 85 degrees C). Under aerobic conditions, growth of lactobacilli was poor and protein hydrolysis did not occur.

Effect of protein concentration, pH, lactose content and pasteurization on thermal gelation of acid caprine whey protein concentrates.

The influence of pH (4.5-6.5), sodium chloride content (125-375 mM), calcium chloride content (10-30 mM), protein concentration (70-90 g/l) and lactose content on the gel hardness of goat whey protein concentrate (GWPC) in relation to the origin of the acid whey (raw or pasteurized milk) was studied using a factorial design.