4 results on '"Arzeni, D."'
Search Results
2. Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer
- Author
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Matassa DS1, Amoroso MR1, Lu H2, Avolio R1, Arzeni D1, Procaccini C3, Faicchia D4, Maddalena F5, Simeon V5, Agliarulo I1, Zanini E2, Mazzoccoli C5, Recchi C2, Stronach E6, Marone G4, Gabra H6, Matarese G1, Landriscina M5, 7, Esposito F1., Matassa, D S, Amoroso, M R, Lu, H, Avolio, R, Arzeni, D, Procaccini, C, Faicchia, D, Maddalena, F, Simeon, V, Agliarulo, I, Zanini, E, Mazzoccoli, C, Recchi, C, Stronach, E, Marone, G, Gabra, H, Matarese, G, Landriscina, M, Esposito, F, Matassa, DANILO SWANN, Amoroso, MARIA ROSARIA, Avolio, Rosario, Procaccini, Claudio, Faicchia, Deriggio, Agliarulo, Ilenia, Marone, Gianni, Matarese, Giuseppe, and Esposito, Franca
- Subjects
0301 basic medicine ,Biochemistry & Molecular Biology ,Programmed cell death ,Bioenergetics ,metabolism ,inflammation ,human ovarian ,cancer ,Cell Survival ,Inflammation ,Biology ,Protein Serine-Threonine Kinases ,Disease-Free Survival ,Oxidative Phosphorylation ,Immediate-Early Proteins ,03 medical and health sciences ,Multidrug Resistance Protein 1 ,Cell Line, Tumor ,medicine ,Humans ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,HSP90 Heat-Shock Proteins ,RNA, Small Interfering ,Molecular Biology ,Cisplatin ,Ovarian Neoplasms ,Original Paper ,Interleukin-6 ,Interleukin-8 ,Cancer ,11 Medical And Health Sciences ,Cell Biology ,06 Biological Sciences ,medicine.disease ,Metformin ,3. Good health ,Cell biology ,030104 developmental biology ,Apoptosis ,Drug Resistance, Neoplasm ,Cancer research ,Tumor necrosis factor alpha ,Female ,RNA Interference ,medicine.symptom ,Glycolysis ,medicine.drug - Abstract
Tumour cells have long been considered defective in mitochondrial respiration and mostly dependent on glycolytic metabolism. However, this assumption is currently challenged by several lines of evidence in a growing number of tumours. Ovarian cancer (OC) is one of the most lethal cancers worldwide, but it continues to be a poorly understood disease and its metabolic features are far to be elucidated. In this context, we investigated the role of tumour necrosis factor receptor-associated protein 1 (TRAP1), which is found upregulated in several cancer types and is a key modulator of tumour cell metabolism. Surprisingly, we found that TRAP1 expression inversely correlated with grade, stage and lower survival in a large cohort of OC patients. Accordingly, TRAP1 silencing induced resistance to cisplatin, resistant cells showed increased oxidative metabolism compared with their sensitive counterpart, and the bioenergetics cellular index of higher grade tumours indicated increased mitochondrial respiration. Strikingly, cisplatin resistance was reversible upon pharmacological inhibition of mitochondrial oxidative phosphorylation by metformin/oligomycin. At molecular level, increased oxidative metabolism in low TRAP1-expressing OC cells and tissues enhanced production of inflammatory mediators such as interleukin (IL)-6 and IL-8. Mechanistically, we identified members of the multidrug resistance complex (MDR) as key mediators of such metabolism-driven, inflammation-induced process. Indeed, treatment of OC cell lines with TNFα and IL6 induced a selective increase in the expression of TAP1 and multidrug resistance protein 1, whereas TAP1 silencing sensitized cells to cisplatin-induced apoptosis. Our results unveil a novel role for TRAP1 and oxidative metabolism in cancer progression and suggest the targeting of mitochondrial bioenergetics to increase cisplatin efficacy in human OC.Cell Death and Differentiation advance online publication, 20 May 2016; doi:10.1038/cdd.2016.39.
- Published
- 2015
3. Antimicrobial Activity of Different Antimicrobial Peptides (AMPs) Against Clinical Methicillin-resistant Staphylococcus aureus (MRSA).
- Author
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Ciandrini E, Morroni G, Arzeni D, Kamysz W, Neubauer D, Kamysz E, Cirioni O, Brescini L, Baffone W, and Campana R
- Subjects
- Anti-Bacterial Agents chemistry, Antimicrobial Cationic Peptides chemistry, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Structure-Activity Relationship, Anti-Bacterial Agents pharmacology, Antimicrobial Cationic Peptides pharmacology, Methicillin-Resistant Staphylococcus aureus drug effects
- Abstract
Background: Antimicrobial research is being focused to look for more effective therapeutics against antibiotic-resistant infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In this direction, antimicrobial peptides (AMP) appear as promising tool., Objectives: This study evaluated the antimicrobial activity of different AMPs (Citropin 1.1, Temporin A, Pexiganan, CA(1-7)M(2-9)NH2, Pal-KGK-NH2, Pal-KKKK-NH2, LL-37) against human MRSA clinical isolates., Methods: The Minimum Inhibitory Concentration (MIC) was assessed for each AMP; then, the most active ones (Citropin 1.1, Temporin A, CA(1-7)M(2-9)NH2 and Pal-KGK-NH2) were tested against selected MRSA strains by time-kill studies., Results: The lowest MIC value was observed for Pal-KGK-NH2 (1 µg/ml), followed by Temporin A (4- 16 µg/ml), CA(1-7)M(2-9)NH2 (8-16 µg/ml) and Citropin 1.1 (16-64 µg/ml), while higher MICs were evidenced for LL-37, Pexiganan and Pal-KKKK-NH2 (> 128 µg/ml). In time-kill experiments, Citropin 1.1 and CA(1-7)M(2-9)NH2 showed a relatively high percentage of growth inhibition (>30 %) for all the tested MRSA clinical isolates, with a dose-dependent activity resulting in the highest percentage of bacterial growth inhibition (89.39%) at 2MIC concentration., Conclusion: Overall, our data demonstrated the potential of some AMPs against MRSA isolates, such as Citropin 1.1 and CA(1-7)M(2-9)NH2, that represents a promising area of development for different clinical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2018
- Full Text
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4. TRAP1 controls cell migration of cancer cells in metabolic stress conditions: Correlations with AKT/p70S6K pathways.
- Author
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Agliarulo I, Matassa DS, Amoroso MR, Maddalena F, Sisinni L, Sepe L, Ferrari MC, Arzeni D, Avolio R, Paolella G, Landriscina M, and Esposito F
- Subjects
- Cell Line, Tumor, Epithelial-Mesenchymal Transition genetics, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, HEK293 Cells, HSP90 Heat-Shock Proteins genetics, Humans, Neoplasm Metastasis, Neoplasms genetics, Neoplasms pathology, Proto-Oncogene Proteins c-akt genetics, Ribosomal Protein S6 Kinases, 70-kDa genetics, Cell Movement, HSP90 Heat-Shock Proteins metabolism, Neoplasms enzymology, Proto-Oncogene Proteins c-akt metabolism, Ribosomal Protein S6 Kinases, 70-kDa metabolism, Signal Transduction, Stress, Physiological
- Abstract
Cell motility is a highly dynamic phenomenon that is essential to physiological processes such as morphogenesis, wound healing and immune response, but also involved in pathological conditions such as metastatic dissemination of cancers. The involvement of the molecular chaperone TRAP1 in the regulation of cell motility, although still controversial, has been recently investigated along with some well-characterized roles in cancer cell survival and drug resistance in several tumour types. Among different functions, TRAP1-dependent regulation of protein synthesis seems to be involved in the migratory behaviour of cancer cells and, interestingly, the expression of p70S6K, a kinase responsible for translation initiation, playing a role in cell motility, is regulated by TRAP1. In this study, we demonstrate that TRAP1 silencing enhances cell motility in vitro but compromises the ability of cells to overcome stress conditions, and that this effect is mediated by the AKT/p70S6K pathway. In fact: i) inhibition of p70S6K activity specifically reduces migration in TRAP1 knock-down cells; ii) nutrient deprivation affects p70S6K activity thereby impairing cell migration only in TRAP1-deficient cells; iii) TRAP1 regulates the expression of both AKT and p70S6K at post-transcriptional level; and iii) TRAP1 silencing modulates the expression of genes involved in cell motility and epithelial-mesenchymal transition. Notably, a correlation between TRAP1 and AKT expression is found in vivo in human colorectal tumours. These results provide new insights into TRAP1 role in the regulation of cell migration in cancer cells, tumour progression and metastatic mechanisms., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
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