P09 Therapeutic potential of NOSH-aspirin, a dual nitric oxide- and hydrogen sulfide-donating hybrid in colon cancer

Nitric Oxide ◽  
2013 ◽  
Vol 31 ◽  
pp. S37-S38
Author(s):  
Mitali Chattopadhyay ◽  
Ravinder Kodela ◽  
Khosrow Kashfi
Keyword(s):  
Nitric Oxide ◽  
Colon Cancer ◽  
Hydrogen Sulfide ◽  
Therapeutic Potential

scholarly journals Vasorelaxant Effect of a New Hydrogen Sulfide-Nitric Oxide Conjugated Donor in Isolated Rat Aortic Rings through cGMP Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Dan Wu ◽  
Qingxun Hu ◽  
Fenfen Ma ◽  
Yi Zhun Zhu
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Cardiovascular Diseases ◽  
Vascular Tone ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Protein Kinase G ◽  
Cgmp Level ◽  
Vasorelaxant Effect ◽  
Cgmp Pathway

Endothelium-dependent vasorelaxant injury leads to a lot of cardiovascular diseases. Both hydrogen sulfide (H2S) and nitric oxide (NO) are gasotransmitters, which play a critical role in regulating vascular tone. However, the interaction between H2S and NO in vasorelaxation is still unclear. ZYZ-803 was a novel H2S and NO conjugated donor developed by H2S-releasing moiety (S-propyl-L-cysteine (SPRC)) and NO-releasing moiety (furoxan). ZYZ-803 could time- and dose-dependently relax the sustained contraction induced by PE in rat aortic rings, with potencies of 1.5- to 100-fold greater than that of furoxan and SPRC. Inhibition of the generations of H2S and NO with respective inhibitors abolished the vasorelaxant effect of ZYZ-803. ZYZ-803 increased cGMP level and the activity of vasodilator stimulated phosphoprotein (VASP) in aortic rings, and those effects could be suppressed by the inhibitory generation of H2S and NO. Both the inhibitor of protein kinase G (KT5823) and the inhibitor of KATPchannel (glibenclamide) suppressed the vasorelaxant effect of ZYZ-803. Our results demonstrated that H2S and NO generation from ZYZ-803 cooperatively regulated vascular tone through cGMP pathway, which indicated that ZYZ-803 had therapeutic potential in cardiovascular diseases.

Therapeutic Potential of Nitric Oxide-Modified Drugs in Colon Cancer Cells

2012 ◽  
Vol 82 (4) ◽  
pp. 700-710 ◽  
Author(s):  
Marija Mojic ◽  
Sanja Mijatovic ◽  
Danijela Maksimovic-Ivanic ◽  
Djordje Miljkovic ◽  
Stanislava Stosic-Grujicic ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Therapeutic Potential ◽  
Colon Cancer Cells

Abstract 3898: NOSH-aspirin: A novel nitric oxide- and hydrogen sulfide-releasing hybrid for treatment of colon cancer

2012 ◽  
Author(s):  
Diana H. Lee ◽  
Diandra E. Nesbitt ◽  
Mitali Chattopadhyay ◽  
Ravinder Kodela ◽  
Khosrow Kashfi
Keyword(s):  
Nitric Oxide ◽  
Colon Cancer ◽  
Hydrogen Sulfide

scholarly journals Emergence of Hydrogen Sulfide as an Endogenous Gaseous Signaling Molecule in Cardiovascular Disease

2014 ◽  
Vol 114 (4) ◽  
pp. 730-737 ◽  
Author(s):  
David J. Polhemus ◽  
David J. Lefer
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Therapeutic Potential ◽  
Rapid Development ◽  
Mammalian Species ◽  
Experimental Studies ◽  
Signaling Molecule ◽  
Organ Systems ◽  
Endogenous Enzymes

Long recognized as a malodorous and highly toxic gas, recent experimental studies have revealed that hydrogen sulfide (H 2 S) is produced enzymatically in all mammalian species including man and exerts several critical actions to promote cardiovascular homeostasis and health. During the past 15 years, scientists have determined that H 2 S is produced by 3 endogenous enzymes and exerts powerful effects on endothelial cells, smooth muscle cells, inflammatory cells, mitochondria, endoplasmic reticulum, and nuclear transcription factors. These effects have been reported in multiple organ systems, and the majority of data clearly indicate that H 2 S produced by the endogenous enzymes exerts cytoprotective actions. Recent preclinical studies investigating cardiovascular diseases have demonstrated that the administration of physiological or pharmacological levels of H 2 S attenuates myocardial injury, protects blood vessels, limits inflammation, and regulates blood pressure. H 2 S has emerged as a critical cardiovascular signaling molecule similar to nitric oxide and carbon monoxide with a profound effect on the heart and circulation. Our improved understanding of how H 2 S elicits protective actions, coupled with the rapid development of novel H 2 S-releasing agents, has resulted in heightened enthusiasm for the clinical translation of this ephemeral gaseous molecule. This review will examine our current state of knowledge about the actions of H 2 S within the cardiovascular system with an emphasis on the therapeutic potential and molecular cross talk between H 2 S, nitric oxide, and carbon monoxide.

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

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