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L-cysteine is currently recognized as a conditionally essential sulphur amino acid. Besides contributing to many biological pathways, cysteine is a key component of the keratin protein by its ability to form disulfide bridges that confer strength and rigidity to the protein. In addition to cysteine, iron represents another critical factor in regulating keratins expression in epidermal tissues, as well as in hair follicle growth and maturation. By focusing on human keratinocytes, the aim of this study was to evaluate the effect of cysteine supplementation as nutraceutical on keratin biosynthesis, as well as to get an insight on the interplay of cysteine availability and cellular iron status in regulating keratins expression in vitro. Herein we demonstrate that cysteine promotes a significant up-regulation of keratins expression as a result of de novo protein synthesis, while the lack of iron impairs keratin expression. Interestingly, cysteine supplementation counteracts the adverse effect of iron deficiency on cellular keratin expression. This effect was likely mediated by the up-regulation of transferrin receptor and ferritin, the main cellular proteins involved in iron homeostasis, at last affecting the labile iron pool. In this manner, cysteine may also enhance the metabolic iron availability for DNA synthesis without creating a detrimental condition of iron overload. To the best of our knowledge, this is one of the first study in an in vitro keratinocyte model providing evidence that cysteine and iron cooperate for keratins expression, indicative of their central role in maintaining healthy epithelia. This article is protected by copyright. All rights reserved.

Many chemotherapeutic drugs cause nucleolar stress and p53-independent pathways mediating the nucleolar stress response are emerging. Here, we demonstrate that ribosomal stress induced by Actinomycin D (Act D) is associated to the up-regulation of ribosomal protein L3 (rpL3) and its accumulation as ribosome-free form in lung and colon cancer cell lines devoid of p53. Free rpL3 regulates p21 expression at transcriptional and post-translational levels through a molecular mechanism involving extracellular-signal-regulated kinases1/2 (ERK1/2) and mouse double minute-2 homolog (MDM2). Our data reveal that rpL3 participates to cell response acting as a critical regulator of apoptosis and cell migration. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of Act D suggesting that the loss of rpL3 makes chemotherapy drugs ineffective while rpL3 overexpression was associated to a strong increase of Act D-mediated inhibition of cell migration. Taking together our results show that the efficacy of Act D chemotherapy depends on rpL3 status revealing new specific targets involved in the molecular pathways activated by Act D in cancers lacking of p53. Hence, the development of treatments aimed at upregulating rpL3 may be beneficial for the treatment of these cancers.

Hybrid Magnetite-gold type nanoparticles with core-shell structure coated by a further outer layer of phospholipids including ruthenium complexes with antitumor activity and peptide sequences, the process 5 for their preparation and their use for simultaneous use as contrast agents for magnetic resonance imaging and as antitumor agents are disclosed

Chemical investigation of the Mediterranean ascidian A.conicum resulted in the isolation of two new meroterpenes, the conithiaquinones A (1) and B (2), in addition to two previously reported chromenols (3 and 4) and conicaquinones (5 and 6). The structures of conithiaquinones A and B were determined by interpretation of spectroscopic data, and regiochemical and stereochemical assignments were achieved with the aid of computational methods, including the recently developed DP4 NMR spectral prediction method. Both conithiaquinones A and B showed significant effects on the growth and viability of cells, with 1 showing interesting cytotoxicity against human breast cancer cells.

La presente invenzione si riferisce al settore delle nanoparticelle e più in particolare a delle nanoparticelle ibride del tipo magnetite-oro con struttura nucleo-guscio (core-shell) funzionalizzate con uno strato esterno di fosfolipidi comprendente ulteriormente complessi di rutenio ad attività antitumorale ed eventualmente sequenze peptidiche, il procedimento per la loro preparazione ed il loro uso per l???impiego simultaneo come agenti di contrasto per le tecniche di diagnostica per immagini e come agenti antitumorali.

The sulphate group is a common feature of echinoderm metabolites, like sulphated saponins with triterpenoid or steroidal aglycones and has also been encountered in sponges’ metabolites, in the form of sulphated sterols and phenol sulphates. Only a few examples of sulfated alkanes/alkenes have been reported from marine sources and, recently, they have been shown to be commonly present in remarkably amounts in Mediterranean tunicates.1 Most of these compounds, often having quite simple structures, are cytotoxic or antimicrobial. More complex polysubstituted alkyl sulfates have also been isolated from ascidians; a remarkable example is turbinamide, a bioactive metabolite isolated few years ago in our laboratory from Sidnyum turbinatum.2 This molecule demonstrated a strong and selective cytotoxic effect against neuronal rather than immune system cells.3 An extensive investigation we have carried out on several species of Mediterranean ascidians evidenced that complex sulphated polyketides are quite widespread in these organisms. We have indeed isolated two new polysubstituted alkyl sulphates from two different Mediterranean ascidians (Sidnyum elegans and Ciona edwardsii) whose structures are referable to that of turbinammide. The new compounds also exhibited a strong cytotoxic activity against C6 glioma cells; their structural analogy with turbinamide allowed also evaluating the influence of slight structural modifications on the activity.

The sulphate group is a common feature of echinoderm metabolites, like sulfated saponins with triterpenoid or steroidal aglycones and has also been encountered in sponges’ metabolites, in the form of sulphated sterols and phenol sulphates. Only a few examples of sulfated alkanes/alkenes have been reported from marine sources and, recently, they have been shown to be commonly present in remarkably amounts in Mediterranean tunicates. Most of these compounds, often having quite simple structures, are cytotoxic or antimicrobial. More complex polysubstituted alkyl sulfates have also been isolated from ascidians; a remarkable example is turbinamide, a bioactive metabolite isolated few years ago in our laboratory from Sidnyum turbinatum. This molecule demonstrated a strong and selective cytotoxic effect against neuronal rather than immune system cells. An extensive investigation we have carried out on several species of Mediterranean ascidians evidenced that complex sulphated polyketides are quite widespread in these organisms. We have indeed isolated two new compounds (1 and 2) very closely related to turbinammide from another collection of S. turbinatum; as well as two new molecules from two different Mediterranean ascidians (Sidnyum elegans and Ciona edwardsii) whose structures are referable to that of turbinammide as well.

Struttura e funzione delle macromole biologiche. Metabolismo e correlazioni metaboliche.

Complex polysubstituted alkyl sulfates have been isolated from ascidians; a remarkable example is turbinamide, a bioactive metabolite isolated in our laboratory from Sidnyum turbinatum. This molecule demonstrated a strong and selective cytotoxic effect against neuronal rather than immune system cells. We have indeed isolated two new sulphated compounds (1 and 2) from another collection of S. turbinatum; as well as two new molecules (3 and 4) from two different Mediterranean ascidians (Sidnyum elegans and Ciona edwardsii). Their structural analogy with turbinamide allowed evaluating the influence of slight structural modifications on the activity.