Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid–nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells

Nitric Oxide ◽  
2008 ◽  
Vol 19 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Sanja Mijatovic ◽  
Danijela Maksimovic-Ivanic ◽  
Marija Mojic ◽  
Graziella Malaponte ◽  
Massimo Libra ◽  
...  
Author(s):  
Ayodeji Folorunsho Ajayi ◽  
Busuyi David Kehinde ◽  
Olubodun Micheal Lateef ◽  
Bolaji Aderibigbe Akorede

Objective: Nitric oxide (NO), prostaglandin E2 (PgE2), and vascular endothelial growth factor (VEGF) are fundamental regulators of epithelial restitution and angiogenesis. They play important roles in ulcer healing. Insights into their possible changes during gastric ulcer healing putting age into consideration could give a guide to the proper management of ulcers in the aging population. This study, therefore, examined alterations in the concentrations of PgE2, NO, and VEGF in the gastric mucosa of rats of different ages after induction of ulcer and during healing.Methods: Male Wister rats (aged 3, 6, and 18 months old) were divided into three groups according to their ages. The ulcer was induced using the acetic acid ulcer model. Healing indices studied on days 3, 7, and 14 were the macroscopic dimension of ulcer, stomach tissue concentration of PgE2, NO, and VEGF, with the immunohistochemical expression of VEGF.Results: Outcome of this study showed 100%, 88.36%, and 62.30% area of mucosa healed in 3-, 6-, and 18-month-old rats respectively, on day 14 post-induction of ulcer. PgE2, NO, and VEGF concentrations were inversely proportional to age during healing. Immunohistochemical staining showed that younger rat (3 and 6 months old) had higher expression of VEGF throughout the healing period.Conclusion: It was therefore concluded that the slower rate of healing in older rats could be due to reduced gastroprotection, epithelial restitution, and angiogenesis as age increases.


2010 ◽  
pp. 443-457
Author(s):  
Sanja Mijatovic ◽  
Danijela Maksimovic-Ivanic ◽  
Marco Donia ◽  
Stanislava Stosic-Grujicic ◽  
Gianni Garotta ◽  
...  
Keyword(s):  

2013 ◽  
Vol 347 (3) ◽  
pp. 607-614 ◽  
Author(s):  
Birandra K. Sinha ◽  
Ashutosh Kumar ◽  
Suchandra Bhattacharjee ◽  
Michael G. Espey ◽  
Ronald P. Mason

2000 ◽  
Vol 114 (5) ◽  
pp. 373-385 ◽  
Author(s):  
Maria Papoutsi ◽  
Gerhard Siemeister ◽  
Karin Weindel ◽  
Stanislav I. Tomarev ◽  
Haymo Kurz ◽  
...  

2018 ◽  
Vol 19 (8) ◽  
pp. 2152 ◽  
Author(s):  
Tzu-Yen Yang ◽  
Mei-Li Wu ◽  
Chi-I Chang ◽  
Chih-I Liu ◽  
Te-Chih Cheng ◽  
...  

Bornyl cis-4-hydroxycinnamate, a bioactive compound isolated from Piper betle stems, has the potential for use as an anti-cancer agent. This study investigated the effects of bornyl cis-4-hydroxycinnamate on cell migration and invasion in melanoma cells. Cell migration and invasion were compared in A2058 and A375 melanoma cell lines treated with/without bornyl cis-4-hydroxycinnamate (1–6 µM). To examine whether bornyl cis-4-hydroxycinnamate has a potential anti-metastatic effect on melanoma cells, cell migration and invasion assays were performed using a Boyden chamber assay and a transwell chamber in A2058 and A375 cells. Gelatin zymography was employed to determine the enzyme activities of MMP-2 and MMP-9. Cell lysates were collected for Western blotting analysis of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), as well as key molecules in the mitogen-activated protein kinase (MAPK), focal adhesion kinase (FAK)/ phosphatidylinositide-3 kinases (PI3K)/Akt/ mammalian target of rapamycin (mTOR), growth factor receptor-bound protein 2 (GRB2) signaling pathways. Our results demonstrated that bornyl cis-4-hydroxycinnamate is a potentially useful agent that inhibits melanoma cell migration and invasion, and altered melanoma cell metastasis by reducing MMP-2 and MMP-9 expression through inhibition of the FAK/PI3K/Akt/mTOR, MAPK, and GRB2 signaling pathways. Moreover, bornyl cis-4-hydroxycinnamate inhibited the process of the epithelial-to-mesenchymal transition in A2058 and A375 melanoma cells. These findings suggested that bornyl cis-4-hydroxycinnamate has potential as a chemotherapeutic agent, and warrants further investigation for its use in the management of human melanoma.


2020 ◽  
Vol 21 (7) ◽  
pp. 2577 ◽  
Author(s):  
Cuizhu Wang ◽  
Yuze Yuan ◽  
He Pan ◽  
Alan Chen-Yu Hsu ◽  
Jinluan Chen ◽  
...  

Gastric ulcer (GU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Finding a natural drug with a gastroprotective effect is needed. Ocotillol, the derivate of ocotillol-type saponins in the Panax genus, possesses good anti-inflammatory activity. The study aimed to investigate the gastroprotective effect of ocotillol on acetic acid-induced GU rats. The serum levels of endothelin-1 (ET-1) and nitric oxide (NO), the gastric mucosa levels of epidermal growth factor, superoxide dismutase and NO were assessed. Hematoxylin and eosin staining of gastric mucosa for pathological changes and immunohistochemical staining of ET-1, epidermal growth factor receptors and inducible nitric oxide synthase were evaluated. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 21 potential metabolites involved in 7 metabolic pathways were identified. The study helps us to understand the pathogenesis of GU and to provide a potential natural anti-ulcer agent.


2020 ◽  
Vol 44 (7-8) ◽  
pp. 381-387
Author(s):  
Mohammad Nur-e-Alam ◽  
Sarfaraz Ahmed ◽  
Muhammad Yousaf ◽  
Shabana I Khan ◽  
Ramzi A Mothana ◽  
...  

Scoparia dulcis L. is one of the edible widely distributed Scropholariaceae species in Asia, Africa and America. It is used in the treatment of respiratory and inflammatory diseases, diabetes, hypertension, cancer, hepatitis and tuberculosis. A phytochemical investigation on S. dulcis led to the isolation of two new acyclic diterpenes Acetic acid 6-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-4,8-dimethyl-undeca-4,8-dienyl ester (1) and Acetic acid 8-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-6,10-dimethyl-undeca-5,9-dienyl ester (2) in addition to eight known compounds (3–10), namely scopadulciol (3), 4- epi-scopadulcic acid B (4), dulcidiol (5), scopadulcic acid B (6), hymenoxin (7), glutinol (8), eupatilin (9) and 5-demethylnobiletin (10). The structures elucidation was performed using spectroscopic means, including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrum spectrometric analysis. Furthermore, the isolated compounds were investigated for their anti-inflammatory activity through the determination of inhibition of nuclear factor-kappa B activity in human chondrosarcoma (SW1353) cells, the inhibition of inducible nitric oxide synthase mouse macrophages (RAW264.7) and the decrease in cellular oxidative stress in HepG2 cells. Moreover, the cytotoxic activity was investigated against four cancer and two kidney cell lines. Among the isolates, 3, 5 and 10 showed anti-inflammatory activity in terms of inhibiting nuclear factor-kappa B and inducible nitric oxide synthase. Compounds 3–5 were the most cytotoxic towards cancer cell lines (IC50: 3.8 µM to 42.3 µM) followed by 10 (IC50: 30.9- > 64.4 µM). Cytotoxicity of compounds 3–5 was comparable to the activity of doxorubicin.


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