Impairment of Nucleolin Activity and Phosphorylation by a Trachylobane Diterpene from in Cancer Cells.

Human nucleolin (hNcl) is a multifunctional protein involved in the progression of various cancers and plays a key role in other pathologies. Therefore, there is still unsatisfied demand for hNcl modulators. Recently, we demonstrated that the plant ent-kaurane diterpene oridonin inhibits hNcl but, unfortunately, this compound is quite toxic for healthy cells.

Genotype-Phenotype Correlation in a Family with Brugada Syndrome Harboring the Novel p.Gln371* Nonsense Variant in the Gene.

Brugada syndrome (BrS) is marked by coved ST-segment elevation and increased risk of sudden cardiac death. The genetics of this syndrome are elusive in over half of the cases. Variants in the gene are the single most common known genetic unifier, accounting for about a third of cases.

Fusicoccane Diterpenes from Hypoestes forsskaolii as Heat Shock Protein 90 (Hsp90) Modulators.

Ten new (1-10) and six known (11-16) fusicoccane diterpenes were isolated from the roots of Hypoestes forsskaolii. The structural characterization of 1-10 was performed by spectroscopic analysis, including 1D and 2D NMR, ECD, and HRESIMS experiments. From a perspective of obtaining potential Hsp90α inhibitors, the isolates were screened by surface plasmon resonance measurements and their cytotoxic activity was assayed using Jurkat and HeLa cancer cells.

The anti-tumor diterpene oridonin is a direct inhibitor of Nucleolin in cancer cells.

The bioactive plant diterpene oridonin displays important pharmacological activities and is widely used in traditional Chinese medicine; however, its molecular mechanism of action is still incompletely described. In vitro and in vivo data have demonstrated anti-tumor activity of oridonin and its ability to interfere with several cell pathways; however, presently only the molecular chaperone HSP70 has been identified as a direct potential target of this compound. Here, using a combination of different proteomic approaches, innovative Cellular Thermal Shift Assay (CETSA) experiments, and classical biochemical methods, we demonstrate that oridonin interacts with Nucleolin, effectively modulating the activity of this multifunctional protein.

Antioxidant Potential of Herbal Preparations and Components from (All.) Nyman ex Soldano.

is a genus of flowering plants belonging to Asteraceae family. This genus is mainly represented by the (All.) Nyman ex Soldano, the milky thistle, a plant of Mediterranean origin.

SIRT1 Activity in Peripheral Blood Mononuclear Cells Correlates with Altered Lung Function in Patients with Chronic Obstructive Pulmonary Disease.

Background: Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease.

New Tirucallane-Type Triterpenoids from Guarea guidonia.

The aerial parts of afforded three new tirucallane-type triterpenoids: 3,4--tirucalla-4(28),8(9),24(25)-trien-7α,11α-dihydroxy-21,23-epoxy-3,11-olide, named guareolide (1: ), 3,4--tirucalla-4(28),7(8),24(25)-trien-21-hydroxy-21,23-epoxy-3-oic acid, named guareoic acid A (2: ), and 3,4--tirucalla-4(28),7(8),24(25)-trien-21,23-epoxy-3-oic acid, named guareoic acid B (3: ), of which 1: possessed an unusual seven-membered lactone ring. Seven known terpenes were also isolated and characterized as flindissone, 7-acetyldihydronomilin, picroquassin E, boscartol C, and cneorubins A, B, and X. Their structures were determined by spectroscopic methods including one-dimensional and two-dimensional nuclear magnetic resonance analysis and high-resolution mass spectrometry.

Cytotoxic triterpenes from Salvia buchananii roots.

A pentacyclic triterpene, named salvibuchanic acid (1), together with five known compounds, were isolated from the roots of Salvia buchananii Hedge (Lamiaceae). The structural characterisation of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR and HRESIMS experiments. The lupane triterpene (1) and hyptadienic acid (2) were investigated for their potential cytotoxic activity on Jurkat, HeLa and MCF7 cell lines.

New Constituents from Gymnocarpos decander.

The phytochemical investigation of aerial parts extract afforded two new saponins, 3---D-glucuronopyranosyl-2,3,16,23-tetrahydroxyolean-12-en-28---D-apiofuranosyl-(1 → 3)--D-xylopyranosyl-(1 → 4)--L-rhamnopyranosyl-(1 → 2)--L-arabinopyranosyl ester (), 3---D-glucuronopyranosyl-2,3,16-trihydroxyolean-12-en-28--α-L-rhamnopyranosyl-(1 → 3)--D-xylopyranosyl-(1 → 4)--L-rhamnopyranosyl-(1 → 2)--L-arabinopyranosyl ester (), and three new flavonol glycosides, isorhamnetin 3--2''''--acetyl--D-xylopyranosyl-(1 → 6)-[-D-apiofuranosyl-(1 → 2)]--D-glucopyranoside (), isorhamnetin 3--2‴--acetyl--D-xylopyranosyl-(1 → 6)--D-glucopyranoside (), and quercetin 3--2‴--acetyl--D-xylopyranosyl-(1 → 6)--D-glucopyranoside (), together with three known compounds. Their structures were determined by spectroscopic methods including 1D and 2D NMR analysis and high-resolution mass spectrometry. The new isolates were investigated for their potential cytotoxic activity on three cancer cell lines.

New sesquiterpene lactones from Ambrosia cumanensis Kunth.

Eleven sesquiterpene lactones, including three new natural products (1-3), were isolated from the n-butanolic extract of Ambrosia cumanensis Kunth. aerial parts. The structure of all isolated compounds was elucidated by 1D- and 2D-NMR, and MS analyses.

BAG3 down-modulation sensitizes HPV18(+) HeLa cells to PEITC-induced apoptosis and restores p53.

BAG3 is a multi-functional component of tumor cell pro-survival machinery, and its biological functions have been largely associated to proteasome system. Here, we show that BAG3 down-modulation resulted in reduced cell viability and enhanced PEITC-induced apoptosis largely more extensively in HeLa (HPV18(+)) rather than in C33A (HPV(-)) cervical carcinoma cell lines. Moreover, we demonstrate that BAG3 suppression led to a decrease of viral E6 oncoprotein and a concomitant recovery of p53 tumor suppressor, the best recognized target of E6 for proteasome degradation.

Bioactive limonoids from the leaves of Azaridachta indica (Neem).

Eight new limonoids (1-8) and one new phenol glycoside (9), along with six known compounds, were isolated from the leaves of Azaridachta indica. The structures of 1-9 were elucidated on the basis of spectroscopic data analysis. Compounds isolated were assayed for their cytotoxicity against different cancer cell lines.

Powerful tumor cell growth-inhibiting activity of a synthetic derivative of atractyligenin: involvement of PI3K/Akt pathway and thioredoxin system.

Background: The semi-synthetic ent-kaurane 15-ketoatractyligenin methyl ester (SC2017) has been previously reported to possess high antiproliferative activity against several solid tumor-derived cell lines. Our study was aimed at investigating SC2017 tumor growth-inhibiting activity and the underlying mechanisms in Jurkat cells (T-cell leukemia) and xenograft tumor models.

Methods: Cell viability was evaluated by MTT assay.

Diterpenes and phenylpropanoids from Clerodendrum splendens.

Four new clerodane diterpenes (1-4) and one new phenylpropanoid (5) have been isolated from Clerodendrum splendens aerial parts, together with nine known compounds. Their structures were determined by spectroscopic and spectrometric analysis and chemical methods. The absolute configuration of the 15,16-diol moiety in 4 was determined by Snatzke's method.

BAG3 protects bovine papillomavirus type 1-transformed equine fibroblasts against pro-death signals.

In human cancer cells, BAG3 protein is known to sustain cell survival. Here, for the first time, we demonstrate the expression of BAG3 protein both in equine sarcoids in vivo and in EqS04b cells, a sarcoid-derived fully transformed cell line harbouring bovine papilloma virus (BPV)-1 genome. Evidence of a possible involvement of BAG3 in equine sarcoid carcinogenesis was obtained by immunohistochemistry analysis of tumour samples.

Chemical proteomics reveals HSP70 1A as a target for the anticancer diterpene oridonin in Jurkat cells.

Unlabelled: Oridonin, an ent-kaurane diterpene isolated from well known Chinese medicinal plant Isodon rubescens, has been shown to have multiple biological activities. Among them, the anticancer activity has been repeatedly reported by many research groups. The chemopreventive and antitumor effects of oridonin have been related to its ability to interfere with several pathways which are involved in cell proliferation, cell cycle arrest, apoptosis and/or autophagy.

A chemical-biological study reveals C9-type iridoids as novel heat shock protein 90 (Hsp90) inhibitors.

The potential of heat shock protein 90 (Hsp90) as a therapeutic target for numerous diseases has made the identification and optimization of novel Hsp90 inhibitors an emerging therapeutic strategy. A surface plasmon resonance (SPR) approach was adopted to screen some iridoids for their Hsp90 α binding capability. Twenty-four iridoid derivatives, including 13 new natural compounds, were isolated from the leaves of Tabebuia argentea and petioles of Catalpa bignonioides.

Properties of the endogenous components of the thioredoxin system in the psychrophilic eubacterium Pseudoalteromonas haloplanktis TAC 125.

The endogenous components of the thioredoxin system in the Antarctic eubacterium Pseudoalteromonas haloplanktis have been purified and characterised. The temperature dependence of the activities sustained by thioredoxin (PhTrx) and thioredoxin reductase (PhTrxR) pointed to their adaptation in the cold growth environment. PhTrxR was purified as a flavoenzyme and its activity was significantly enhanced in the presence of molar concentration of monovalent cations.

Anti-angiogenic activity evaluation of secondary metabolites from Calycolpus moritzianus leaves.

Angiogenesis is a crucial step in many pathological conditions like cancer, inflammation and metastasis formation; on these basis the search for antiangiogenic agents has widened. In order to identify new compounds able to interfere in the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1, also known as Flt-1) recognition by VEGFs family members, we screened Calycolpus moritzianus (O. Berg) Burret leaves extracts by a competitive ELISA-based assay.

Phenolic compounds from the roots of Jordanian viper's grass, Scorzonera judaica.

Nine new phenolic compounds, 3S-hydrangenol 40-O-R-L-rhamnopyranoysl-(1-->3)-β-D-glucopyranoside (1), thunberginol F 7-O-β-D-glucopyranoside (2), 2-hydroxy-6-[2-(4-hydroxyphenyl)-2-oxo-ethyl]benzoic acid (3), 2-hydroxy-6-[2-(3,4-dihydroxyphenyl)-2-oxo-ethyl]benzoic acid (4), 2-hydroxy-6-[2-(3,4-dihydroxyphenyl-5-methoxy)-2-oxoethyl]benzoic acid (5), hydrangeic acid 40-O-β-D-glucopyranoside (6), E-3-(3,4-dihydroxybenzylidene)-5-(3,4-dihydroxyphenyl)dihydrofuran-2-one (7), Z-3-(3,4-dihydroxybenzylidene)-5-(3,4-dihydroxyphenyl)-2(3H)-furanone (8), and 4-[β-D-glucopyranosyl)hydroxy]-pinoresinol (9), and nine known compounds were isolated from the roots of Scorzonera judaica. Structures of 1-9 were elucidated by mass spectrometry, extensive 1D and 2D NMR spectroscopy, and CD spectroscopy.All compounds were evaluated for cytotoxic activity.

Rimonabant-induced apoptosis in leukemia cell lines: activation of caspase-dependent and -independent pathways.

Rimonabant (SR141716), a cannabinoid CB1 receptor antagonist known for anti-obesity activity, has more recently been shown to inhibit tumor cell growth. Here we demonstrated the antitumor potential of SR141716 in leukemia-derived cell lines and its low toxicity in normal cells (PBMC). SR141716 (1-20microM range of doses) reduced Jurkat and U937 cell number by activating death signals as well as affecting cell cycle progression.

Rat mitochondrial manganese superoxide dismutase: amino acid positions involved in covalent modifications, activity, and heat stability.

The role of three amino acid residues (Q143, Y34, S82) of rat mitochondrial superoxide dismutase (ratSOD2) in the enzymatic activity, thermostability, and post-translational modification of the enzyme was investigated through site-directed mutagenesis studies. Six recombinant forms of the enzyme were produced, carrying the Q143 or H143 residue with or without the Y34F or S82A replacement. All proteins bound manganese as active cofactor and were organized as homotetramers.

Differential cold-adaptation among protein components of the thioredoxin system in the psychrophilic eubacterium Pseudoalteromonas haloplanktis TAC 125.

Thioredoxin and thioredoxin reductase from the psychrophilic eubacterium Pseudoalteromonas haloplanktis were obtained as recombinant His-tagged proteins (rPhTrx and rPhTrxR, respectively). rPhTrxR is organised as a homodimeric flavoenzyme, whereas rPhTrx is a small monomeric protein, both containing a functional disulfide bridge. However, three additional cysteines are present as free thiols in purified rPhTrxR.

Adaptation of model proteins from cold to hot environments involves continuous and small adjustments of average parameters related to amino acid composition.

The growth temperature adaptation of six model proteins has been studied in 42 microorganisms belonging to eubacterial and archaeal kingdoms, covering optimum growth temperatures from 7 to 103 degrees C. The selected proteins include three elongation factors involved in translation, the enzymes glyceraldehyde-3-phosphate dehydrogenase and superoxide dismutase, the cell division protein FtsZ. The common strategy of protein adaptation from cold to hot environments implies the occurrence of small changes in the amino acid composition, without altering the overall structure of the macromolecule.