0000000000199576
AUTHOR
Pietro Campiglia
Overcome Chemoresistance: Biophysical and Structural Analysis of Synthetic FHIT-Derived Peptides.
The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. On the basis of genetic evidence, it has been postulated that the FHIT protein may function as tumor suppressor, implying a role for the FHIT protein in carcinogenesis. Recently, Gaudio et al. reported that FHIT binds and delocalizes annexin A4 (ANXA4) from plasma membrane to cytosol in paclitaxel-resistant lung cancer cells, thus restoring their chemosensitivity to the drug. They also identified the smallest protein sequence of the FHIT still interacting with ANXA4, ranging from position 7 to 13: QHLIKPS. This short sequence of FHIT protein was not only able to bind …
Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors
Cyclooxygenase (COX) is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation. It exists mainly in two isoforms COX-1 and COX-2. The conventional nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects because they inhibit both isoforms. Recent data demonstrate that the overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that the inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Agents that inhibit COX-2 while sparing COX-1 represent a new attractive therapeutic deve…
Anti-inflammatory and antioxidant activity of polyphenolic extracts from Lactuca sativa (var. Maravilla de Verano ) under different farming methods
BACKGROUND Besides their nutritional value, vegetables are a source of health-promoting compounds, such as polyphenols, and their content can be influenced by the particular farming method. In this study polyphenolic extracts from Lactuca sativa (var. Maravilla de verano) plants cultivated with different farming methods were chemically characterised and tested in vitro and ex vivo inflammation models. RESULTS The tested extacts (250–2.5 µg mL−1) were able to reduce both the inflammatory and oxidative stress in LPS-stimulated J774A.1 murine monocyte macrophage cells, by lowering the release of nitric oxide (NO) and reactive oxygen species (ROS) and promoting nuclear translocation of nuclear …
Amino Acid derivatives as new zinc binding groups for the design of selective matrix metalloproteinase inhibitors.
A number of matrix metalloproteinases (MMPs) are important medicinal targets for conditions ranging from rheumatoid arthritis to cardiomyopathy, periodontal disease, liver cirrhosis, multiple sclerosis, and cancer invasion and metastasis, where they showed to have a dual role, inhibiting or promoting important processes involved in the pathology. MMPs contain a zinc (II) ion in the protein active site. Small-molecule inhibitors of these metalloproteins are designed to bind directly to the active site metal ions. In an effort to devise new approaches to selective inhibitors, in this paper, we describe the synthesis and preliminary biological evaluation of amino acid derivatives as new zinc b…
Potential anticarcinogenic peptides from bovine milk.
Bovine milk possesses a protein system constituted by two major families of proteins: caseins (insoluble) and whey proteins (soluble). Caseins (αS1,αS2,β, andκ) are the predominant phosphoproteins in the milk of ruminants, accounting for about 80% of total protein, while the whey proteins, representing approximately 20% of milk protein fraction, includeβ-lactoglobulin,α-lactalbumin, immunoglobulins, bovine serum albumin, bovine lactoferrin, and lactoperoxidase, together with other minor components. Different bioactivities have been associated with these proteins. In many cases, caseins and whey proteins act as precursors of bioactive peptides that are released, in the body, by enzymatic pro…
β-Lactoglobulin Heptapeptide Reduces Oxidative Stress in Intestinal Epithelial Cells and Angiotensin II-Induced Vasoconstriction on Mouse Mesenteric Arteries by Induction of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Translocation
Peptides derived from buffalo dairy products possess multiple healthy properties that cannot be exerted as long as they are encrypted in parent proteins. To evaluate the biological activities of encrypted peptide sequences from buffalo ricotta cheese, we performed a simulated gastrointestinal (GI) digestion. Chemical and pharmacological characterization of the digest led to the identification of a novel peptide endowed with antioxidant and antihypertensive action. The GI digest was fractionated by Semiprep-HPLC, and fractions were tested against reactive oxygen species (ROS) release in an H2O2-treated intestinal epithelial cell line. UHPLC-PDA-MS/MS analysis revealed the presence of an abun…
Analysis of the metabolic switch induced by the spirulina peptide SP6 in high fat diet ApoE-/-mice model: A direct infusion FT-ICR-MS based approach
Atherosclerosis, dyslipidemia and hypertension are comorbid diseases often found in combination. Among different pharmacological approaches the employment of natural multifunctional peptides is an attractive option as side therapy. Mass spectrometry-based metabolomics provide valuable information on metabolic changes and can be useful to elucidate peptide pharmacodynamics. In this this work we performed a preliminary investigation on the potential effect of a recently characterized Spirulina platensis peptide named SP6 (GIVAGDVTPI) on the modulation of metabolism in a high fat diet ApoE-/- mice atherosclerotic model. A direct infusion Fourier transform ion cyclotron resonance mass spectrome…
Hop-derived fraction rich in beta acids and prenylflavonoids regulates the inflammatory response in dendritic cells differently from quercetin: unveiling metabolic changes by mass spectrometry-based metabolomics.
Dendritic cells (DCs) represent a heterogeneous family of immune cells that link innate and adaptive immunity and their activation is linked to metabolic changes that are essential to support their activity and function. Hence, targeting the metabolism of DCs represents an opportunity to modify the inflammatory and immune response. Among the natural matrices, Humulus lupulus (Hop) compounds have recently been shown to exhibit immunomodulatory and anti-inflammatory activity. This study aimed to evaluate the ability of specific Hop fractions to modulate DCs metabolism after stimulation with lipopolysaccharide (LPS) by an untargeted metabolomics approach and compare their effect with flavonol …
Polyphenolic Extract from Tarocco (Citrus sinensis L. Osbeck) Clone "Lempso" Exerts Anti-Inflammatory and Antioxidant Effects via NF-kB and Nrf-2 Activation in Murine Macrophages.
Citrus fruits are often employed as ingredients for functional drinks. Among Citrus, the variety, “Lempso„, a typical hybrid of the Calabria region (Southern Italy), has been reported to possess superior antioxidant activity when compared to other common Citrus varieties. For these reasons, the aim of this study is to investigate in vitro the nutraceutical value of the Tarocco clone, “Lempso„, highlighting its anti-inflammatory and antioxidant potential. A post-column 2,2′-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging assay for the screening of antioxidant compounds in these complex matrices was developed. Subsequently, polyphenolic extract was tes…
Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies
Abstract: The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols. In the present study, we demonstrated that smoothies containing mixtures of Citrus sinensis and Vitis vinifera L. cv. Aglianico N, two typical fruits of the Mediterranean diet, possess bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress. The polyphenolic extracts isolated from Citrus sinensis- and Vitis vinifera-based functional smoothies were deeply characterized by Liquid Chromatography-Mass Spectrometry methods. Subsequently, the functional smoothies and relative mixtures were tested to verify their ab…
Nobiletin and xanthohumol sensitize colorectal cancer stem cells to standard chemotherapy
Simple Summary Colorectal cancer stem cells (CR-CSCs) play a pivotal role in the therapy resistance and relapse of CRC patients. Herein we demonstrate that new treatment approaches comprising polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively, hamper the viability of CR-CSCs as well as synergizing with 5-fluorouracil and oxaliplatin (FOX)-based chemotherapy. Extract fractions containing Nobiletin and Xanthohumol, in combination with chemotherapy, decreased stemness properties of CR-CSCs and restrained the outgrowth of chemoresistant metastatic CR-CSCs. These data pinpoint Nobiletin and Xanthohumol as efficacious anti-cancer compounds in…
Metabolomics-assisted discovery of a new anticancer GLS-1 inhibitor chemotype from a nortopsentin-inspired library: From phenotype screening to target identification
The enzyme glutaminase-1 (GLS-1) has shown a clear and coherent implication in the progression and exacerbation of different aggressive tumors such as glioblastoma, hepatocarcinoma, pancreas, bone, and triple-negative breast cancer. Few chemotypes are currently available as selective GLS-1 inhibitors, and still, fewer of them are at the clinical stage. In the present paper, starting from a naturally-inspired antitumor compound library, metabolomics has been used to putatively identify the molecular mechanism underlying biological activity. GLS-1 was identified as a potential target. Biochemical analysis confirmed the hypothesis leading to the identification of a new hit compound acting as a…
Bioactive Polyphenols from Pomegranate Juice Reduce 5-Fluorouracil-Induced Intestinal Mucositis in Intestinal Epithelial Cells
Intestinal epithelial cells (IECs) play a pivotal role in maintaining intestinal homeostasis. Different noxious agents, among them also anticancer therapies, can impair intestinal epithelial integrity triggering inflammation and oxidative stress. A frequent complication of chemotherapy is gastrointestinal mucositis, strongly influencing the effectiveness of therapy, increasing healthcare costs, and impairing patients&rsquo
Immunomodulatory activity of Humulus lupulus bitter acids fraction: Enhancement of natural killer cells function by NKp44 activating receptor stimulation
Abstract Humulus lupulus (Hop) contains numerous metabolites with anticancer potential. Despite this, their immunomodulatory activity, and in particular of bitter acids, is unknown. In this study, we demonstrated that a Hop pellet extract fraction containing bitter acids possesses immunomodulatory activity by enhancing Natural Killer (NK) cells function. After fractionation by semi-preparative Liquid Chromatography, three different fractions were obtained. The phytocomplex and the fractions were tested to verify the ability to modulate the NK compartment. Cytofluorimetric analysis revealed that a fraction containing bitter acids was able to up-regulate of NKG2D and NKp44 activating receptor…