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Francisco Madariaga-Venegas, Roberto Fernández-Soto, Luisa Fernanda Duarte, Nicole Suarez, Daniela Delgadillo, José A Jara, Ricardo Fernández-Ramires, Blanca Urzúa, Alfredo Molina-Berríos
Candida albicans biofilms play a key role in denture stomatitis, one of the most common oral pathologies in elderly people. Because biofilms are highly resistant to antifungals, new pharmacological strategies are needed. Aspirin and nitric oxide-donor molecules have both shown antibiofilm effects on C. albicans, making them promising candidates for treatment. In this study, we evaluated the antifungal/antibiofilm effect of a nitric-oxide releasing aspirin (NO-ASA) on C. albicans isolates from denture stomatitis patients in vitro...
2017: PloS One
Eun-Young Choi, So-Hui Choe, Jin-Yi Hyeon, Hae Ryoun Park, Jeom-Il Choi, In Soon Choi, Sung-Jo Kim
In this study, the effects and underlying mechanisms of NCX 4040, a nitric oxide (NO)-donating aspirin derivative, on the production of proinflammatory mediators were examined using murine macrophages exposed to lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in the etiology of periodontal disease. NCX 4040 significantly reduced P. intermedia LPS-induced production of inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. Notably, NCX 4040 was much more effective than the parental compound aspirin in reducing LPS-induced production of inflammatory mediators...
December 5, 2015: European Journal of Pharmacology
Tareisha Dunlap, Sujeewa C Piyankarage, Gihani T Wijewickrama, Samer Abdul-Hay, Michael Vanni, Vladislav Litosh, Jia Luo, Gregory R J Thatcher
The promising therapeutic potential of the NO-donating hybrid aspirin prodrugs (NO-ASA) includes induction of chemopreventive mechanisms and has been reported in almost 100 publications. One example, NCX-4040 (pNO-ASA), is bioactivated by esterase to a quinone methide (QM) electrophile. In cell cultures, pNO-ASA and QM-donating X-ASA prodrugs that cannot release NO rapidly depleted intracellular GSH and caused DNA damage; however, induction of Nrf2 signaling elicited cellular defense mechanisms including upregulation of NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase (GCL)...
December 17, 2012: Chemical Research in Toxicology
Emanuela Ricciotti, Melania Dovizio, Luigia Di Francesco, Paola Anzellotti, Tania Salvatore, Andrea Di Francesco, Maria G Sciulli, Giuseppa Pistritto, Angela Monopoli, Paola Patrignani
NO-donating aspirins consist of aspirin to which a NO-donating group is covalently linked via a spacer molecule. NCX 4040 and NCX 4016 are positional isomers with respect to the -CH(2)ONO(2) group (para and meta, respectively) on the benzene ring of the spacer. Because positional isomerism is critical for antitumor properties of NO-donating aspirins, we aimed to compare their anti-inflammatory effects with those of aspirin in vitro. Thus, we assessed their impacts on cyclooxygenase-2 activity (by measuring PGE(2) levels), protein expression, and cytokine generation(IL-1beta, IL-18, TNF-alpha, and IL-10) in human whole blood and isolated human monocytes stimulated with LPS...
February 15, 2010: Journal of Immunology: Official Journal of the American Association of Immunologists
Biljana Bufan, Slavko Mojsilović, Dragana Vucićević, Dragana Vucević, Sasa Vasilijić, Bela Balint, Miodrag Colić
Acetylsalicilyc acid (aspirin, ASA) is a well known anti-inflammatory drug with immunomodulatory properties. NO-releasing aspirins (NO-ASA) are new compounds with anti-inflammatory properties. We studied the effects of ASA and two NO-ASA (NCX 4016 and NCX 4040) on human monocyte-derived dendritic cells (MoDC). Immature MoDC were generated in vitro from monocytes in the presence of recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4. Mature MoDC were obtained by adding lipopolysaccharide (LPS) in cultures of immature MoDC...
July 2009: International Immunopharmacology
Tareisha Dunlap, Samer O Abdul-Hay, R Esala P Chandrasena, Ghenet K Hagos, Vaishali Sinha, Zhiqiang Wang, Huali Wang, Gregory R J Thatcher
Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than one hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors...
September 2008: Nitric Oxide: Biology and Chemistry
Anna Tesei, Wainer Zoli, Francesco Fabbri, Carlo Leonetti, Marco Rosetti, Manlio Bolla, Dino Amadori, Rosella Silvestrini
Non-steroidal anti-inflammatory drugs (NSAIDs) have repeatedly shown to be effective in tumor prevention, but important side-effects limit their wide clinical use. Nitric oxide-releasing derivatives (NO-NSAIDs) are a promising class of compounds synthesized by combining a classic NSAID molecule with an NO-releasing moiety to counteract side-effects. These new chemical entities exhibit a significantly higher activity and much lower toxicity with respect to the parental drug. In the present paper, we report the results obtained from in in vitro experimental systems aimed to evaluate the activity and mechanisms of action of the novel NO-releasing aspirin derivative, NCX 4040...
September 2008: Nitric Oxide: Biology and Chemistry
Anna Bratasz, Karuppaiyah Selvendiran, Tomasz Wasowicz, Andrey Bobko, Valery V Khramtsov, Louis J Ignarro, Periannan Kuppusamy
BACKGROUND: Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. The high mortality rate is associated with lack of early diagnosis and development of drug resistance. The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied. METHODS: NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP), was studied in cisplatin-sensitive (A2780 WT) and cisplatin-resistant (A2780 cDDP) cell lines as well as xenograft tumors grown in nude mice...
February 26, 2008: Journal of Translational Medicine
Tareisha Dunlap, R Esala P Chandrasena, Zhiqiang Wang, Vaishali Sinha, Zhican Wang, Gregory R J Thatcher
Cellular defense mechanisms that respond to damage from oxidative and electrophilic stress, such as from quinones, represent a target for chemopreventive agents. Drugs bioactivated to quinones have the potential to activate antioxidant/electrophile responsive element (ARE) transcription of genes for cytoprotective phase 2 enzymes such as NAD(P)H-dependent quinone oxidoreductase (NQO1) but can also cause cellular damage. Two isomeric families of compounds were prepared, including the NO-NSAIDs (NO-donating nonsteroidal anti-inflammatory drugs) NCX 4040 and NCX 4016; one family was postulated to release a quinone methide on esterase bioactivation...
December 2007: Chemical Research in Toxicology
Anna Tesei, Marco Rosetti, Paola Ulivi, Francesco Fabbri, Laura Medri, Ivan Vannini, Manlio Bolla, Dino Amadori, Wainer Zoli
BACKGROUND: Despite numerous studies aimed at verifying the antitumor activity of nitric oxide-releasing nonsteroidal antiflammatory drugs (NO-NSAIDs), little is known about the molecular targets responsible for their antineoplastic properties. In the present study, we investigated the mechanisms underlying the cytotoxicity of NCX 4040, a novel NO-aspirin with promising antineoplastic action, in in vitro human colon cancer models. METHODS: The effect on tumor growth was evaluated in four human colon cancer cell lines (LoVo, LRWZ, WiDr and LoVo Dx) by sulforhodamine B assay, oxidative stress by immunohistochemistry, apoptosis by laddering assay, mitochondrial membrane potential (DeltaPsim) by flow cytometry, and apoptosis- and chemoresistance-related markers by western-blot and real-time method, respectively...
2007: Journal of Translational Medicine
Marco Rosetti, Anna Tesei, Paola Ulivi, Francesco Fabbri, Ivan Vannini, Giovanni Brigliadori, Dino Amadori, Manlio Bolla, Wainer Zoli
Although non steroidal antiinflammatory drugs (NSAIDs) have been shown to be effective as chemopreventive agents, important side-effects limit their clinical use. A promising novel class of drugs, nitric oxide-donating NSAIDs (NO-NSAIDs), has been found to be more active than classical NSAIDs. This study explored the effect of the NO-donating aspirin derivative, NCX 4040, on three human pancreatic adenocarcinoma cell lines (Capan-2, MIA PaCa-2 and T3M4). NCX 4040 activity was compared with that of NCX 4016 (an NO(2)-positional isomer of NCX 4040), SNAP (a standard NO-releasing molecule), NCX 4042 (denitrated analog of NCX 4040), and aspirin...
August 2006: Apoptosis: An International Journal on Programmed Cell Death
Carlo Leonetti, Marco Scarsella, Gabriella Zupi, Wainer Zoli, Dino Amadori, Laura Medri, Francesco Fabbri, Marco Rosetti, Paola Ulivi, Lorenzo Cecconetto, Manlio Bolla, Anna Tesei
We previously showed that NCX 4040 inhibits in vitro and in vivo tumor growth and induces apoptosis in human colon cancer cell lines. On the basis of these results, NCX 4040 antitumor activity in combination with 5-fluorouracil (5-FU) or oxaliplatin was evaluated in vitro and in vivo in human colon cancer models. The cytotoxicity of different NCX 4040 and 5-FU or oxaliplatin combination schemes was evaluated on a panel of colon cancer lines (LoVo, LoVo Dx, WiDr, and LRWZ) by the sulforhodamine B assay, and apoptosis was assessed by flow cytometry...
April 2006: Molecular Cancer Therapeutics
Xin-Hua Zhang, Sandra Filippi, Annamaria Morelli, Linda Vignozzi, Michaela Luconi, Silvia Donati, Gianni Forti, Mario Maggi
INTRODUCTION: Hypogonadism is often associated with diabetes and both conditions represent major risk factors for erectile dysfunction (ED). AIM: To investigate the role of hypogonadism on phosphodiesterase type 5 (PDE5) expression and sildenafil responsiveness in diabetes. METHODS: Two different models of experimental diabetes were used: (i) alloxan-induced diabetic rabbit; and (ii) streptozotocin (STZ)-induced diabetic rat. In both experimental models, animals were separated into three groups: control, diabetic, diabetic supplemented with testosterone (T) enanthate...
March 2006: Journal of Sexual Medicine
F Fabbri, G Brigliadori, P Ulivi, A Tesei, I Vannini, M Rosetti, S Bravaccini, D Amadori, M Bolla, W Zoli
Nitric oxide-releasing non steroidal anti-inflammatory drugs (NO-NSAIDs) are a promising class of compounds that cause cell cycle perturbations and induce apoptosis in cell lines from different tumors. We investigated the activity of a recently developed NO-NSAID (NCX 4040) in bladder cancer cell lines (HT1376 and MCR). Cells were treated with different drug concentrations for different exposure times. Cytostatic and cytocidal activity was tested by SRB assay and apoptosis was evaluated by TUNEL analysis, ANNEXIN V assay and fluorescence microscopy...
October 2005: Apoptosis: An International Journal on Programmed Cell Death
Anna Tesei, Paola Ulivi, Francesco Fabbri, Marco Rosetti, Carlo Leonetti, Marco Scarsella, Gabriella Zupi, Dino Amadori, Manlio Bolla, Wainer Zoli
BACKGROUND: Nitric oxide-releasing nonsteroidal antiinflammatory drugs (NO-NSAIDs) are reported to be safer than NSAIDs because of their lower gastric toxicity. We compared the effect of a novel NO-releasing derivate, NCX 4040, with that of aspirin and its denitrated analog, NCX 4042, in in vitro and in vivo human colon cancer models and investigated the mechanisms of action underlying its antitumor activity. METHODS: In vitro cytotoxicity was evaluated on a panel of colon cancer lines (LoVo, LoVo Dx, WiDr and LRWZ) by sulforhodamine B assay...
February 3, 2005: Journal of Translational Medicine
Saima Muzaffar, Nilima Shukla, Gianni Angelini, Jamie Y Jeremy
BACKGROUND: Although nonsteroidal antiinflammatory drugs (NSAIDs) are ineffective in treating acute respiratory distress syndrome (ARDS), inhalational NO has proved to be useful. NO-donating NSAIDs may therefore be more effective in treating ARDS than NSAIDs alone. Because oxidant stress is central to the pathophysiology of ARDS, the effect of nitroaspirins (NCX 4016, NCX 4040, and NCX 4050) compared with morpholinosydnonimine (SIN-1; an NO donor) and aspirin (ASA) on superoxide (O2*-) formation and gp91phox (an active catalytic subunit of NADPH oxidase) expression in pig pulmonary artery vascular smooth muscle cells (PAVSMCs) and endothelial cells (PAECs) was investigated...
August 31, 2004: Circulation
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