Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy.

Abstract	Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds.
Authors	Shoucheng Ning, Mark Bednarski, Bryan Oronsky, Jan Scicinski, Susan J Knox
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 447 Issue 3 Pg. 537-42 (May 09 2014) ISSN: 1090-2104 [Electronic] United States
PMID	24735538 (Publication Type: Journal Article)
Copyright	Copyright © 2014 Elsevier Inc. All rights reserved.
Chemical References	Benzoates Epoxy Compounds Imidazoles Nitrates Nitric Oxide Donors Radiation-Sensitizing Agents glycidyl nitrate 1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole Nitric Oxide
Topics	Animals Benzoates (pharmacology) Cell Line, Tumor Drug Resistance, Neoplasm (drug effects) Epoxy Compounds (therapeutic use) HT29 Cells Humans Imidazoles (pharmacology) Male Mice Mice, Inbred C3H Neoplasms (blood supply, drug therapy, radiotherapy, therapy) Nitrates (therapeutic use) Nitric Oxide (metabolism) Nitric Oxide Donors (therapeutic use) Radiation-Sensitizing Agents (therapeutic use) Regional Blood Flow (drug effects)

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