No abstract

No abstract

No abstract

Triterpene glycosides are characteristic metabolites of sea cucumbers (Holothurioidea, Echinodermata). Majority of the glycosides belong to holostane type (lanostane derivatives with 18(20)-lactone). Carbohydrate chains of these glycosides contain xylose, glucose, quinovose, 3-O-methylglucose and 3-O-methylsylose. During the last 5 years, main investigations were focused on holothurians belonging to the order Dendrochirotida collected in the North Pacific, North Atlantic, Antarctic and in subtropical waters. The glycosides of holothurians belonging to the order Aspidochirotida have also been studied. The most uncommon structural features of carbohydrate chains of new glycosides were: (1) the presence of quinovose as fifth terminal monosaccharide unit and the presence of two quinovose residues; (2) the presence of glucose instead of common xylose as fifth terminal monosaccharide unit; (3) trisaccharide carbohydrate chain; (4) the presence of two 3-O-methylxylose terminal monosaccharide units; (5) the presence of sulfate group at C-3 of quinovose residue. New glycosides without lactone or with 18(16)-lactone and having shortened side chains have also been isolated. The presence of 17a and 12a-hydroxyls, which are characteristic for glycosides from holothurians belonging to the family Holothuriidae (Aspidochirotida) in glycosides of dendrochirotids confirms parallel and relatively independent character of evolution of glycosides. All three families belonging to the order Aspidochirotida: Holothuriidae, Stichopodidae and Synallactidae have similar and parallel trends in evolution of the glycosides carbohydrate chains, namely from nonsulfated hexaosides to sulfated tetraosides. Sets of aglycones in glycosides from holothurians belonging to the genus Cucumaria (Cucumariidae, Dendrochirotida) are specific for each species. The carbohydrate chains are similar in all representatives of the genus Cucumaria.

Monanchocidin (1), a guanidine alkaloid with an unprecedented skeleton system derived from a polyketide precursor, (ω-3)-hydroxy fatty acid, and containing a 2-aminoethyl- and 3-aminopropyl-substituted morpholine hemiketal ring, has been isolated from the sponge Monanhora pulchra. The structure of 1 was assigned on the basis of detailed analysis of 1D and 2D NMR spectra, mass spectrometry, and results of chemical transformations. Compound 1 shows pro-apoptotic and cytoxic activities.

No abstract

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), outcome of patients remains poor due to the development of drug resistance. Thus, new drugs are urgently needed. We investigated efficacy, toxicity and mechanism of action of marine triterpene glycoside frondoside A (FrA) using CRPC cell lines in vitro and in vivo. FrA revealed high efficacy in human prostate cancer cells, while non-malignant cells were less sensitive. Remarkably, proliferation and colony formation of cells resistant to enzalutamide and abiraterone (due to the androgen receptor splice variant AR-V7) were also significantly inhibited by FrA. The marine compound caused cell type specific cell cycle arrest and induction of caspase-dependent or -independent apoptosis. Up-regulation or induction of several pro-apoptotic proteins (Bax, Bad, PTEN), cleavage of PARP and caspase-3 and down-regulation of anti-apoptotic proteins (survivin and Bcl-2) were detected in treated cells. Global proteome analysis revealed regulation of proteins involved in formation of metastases, tumor cell invasion, and apoptosis, like keratin 81, CrkII, IL-1b and cathepsin B. Inhibition of pro-survival autophagy was observed following FrA exposure. In vivo, FrA inhibited tumor growth of PC-3 and DU145 cells with a notable reduction of lung metastasis, as well as circulating tumor cells in the peripheral blood. Increased lymphocyte counts of treated animals might indicate an immune

Skin can age in two ways: (i) intrinsic or chronologic aging, which is the process of senescence that affects all body organs; and (ii) extrinsic aging which occurs as a consequence of exposure to environmental factors including sunlight and cigarette smoke. 1)The most important of these factors is sunlight, particularly exposure to ultraviolet (UV)B irradiation, which causes photoaging. The photoaging process increases skin fragility, laxity, blister formation, leathery appearance and formation of wrinkles. 2)UVB induces the production of matrix metalloproteinases (MMPs) by activating cellular signaling transduction pathways 3) ; MMPs are responsible for the degradation or synthesis inhibition of collagenous extracellular matrix in connective tissues.3) Collagen represents the main component of the extracellular matrix of dermal connective tissue, and its concentration decreases in chronoaging and photoaging.All matrix macromolecules in the dermis can be digested by MMPs acting alone or in combination. The MMPs form a family of structurally and functionally related zinc endopeptidases that exhibit various substrate specificities. 4) Once collagen is initially cleaved by MMP-1, MMP-3 and other MMPs, collagen breakdown is further promoted. The enzyme mainly responsible for collagen breakdown in skin is, MMP-1 (fibroblast collagenase), which cleaves type I, III, VII, VIII and X collagen.Human fibroblast collagenase was the first vertebrate collagenase both purified to homogeneity as a protein, and cloned as a cDNA. This enzyme has been designated as matrix metalloproteinase-1 (MMP-1) and has served as the prototype for all the interstitial collagenases. MMP-1 is also known as collagenase-1. Starting from the N terminus the following features of domain organization are observed. 5)The pre-domain specifies a signal rich in hydrophobic amino acids that destines the synthesized polypeptide to the endoplasmic reticulum where it is removed during the transportation of the molecule from the cell to the outside. The propeptide domain indicates a sequence that is responsible of keeping the pro-form inactive. It presents a cysteine residue 73 that is located in a conserved sequence PRCGVPD opposite to a zinc atom at the active-form site and coordinated to it through an -SH group. The enzymatic activity of the proform enzyme is turned on by the displacement of this cysteine residue ("cysteine switch") and occurs by proteolytic cleavage, or by chemical disruption as in the case of oxidation or treatment with mercurial compounds. 6)Recent studies have shown that hairless mice exposed to UVB developed wrinkled skin and significantly enhanced MMP-1 mRNA expression. However, they have shown that the inihibition of MMP-1 activities by a specific MMP inhibitor suppresses UVB-induced wrinkle formation.7) This evidence suggests that MMP-1 plays a major role in the process of photoaging.Brown seaweed has been a staple of both Korean and Japanese diets and has also been documented as being used in traditional Chinese medicine for over ...