Publication:
Nitrite may serve as a combination partner and a biomarker for the anti-cancer activity of RRx-001

dc.contributor.coauthorCirrik, Selma
dc.contributor.coauthorOronsky, Bryan
dc.contributor.coauthorCabrales, Pedro
dc.contributor.departmentSchool of Medicine
dc.contributor.departmentGraduate School of Health Sciences
dc.contributor.kuauthorAksu, Ali Cenk
dc.contributor.kuauthorUğurel, Elif
dc.contributor.kuauthorYalçın, Özlem
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF HEALTH SCIENCES
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T23:51:35Z
dc.date.issued2019
dc.description.abstractBackground: RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. Objective: In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. Methods: A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. Results: Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). Conclusions: Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue4
dc.description.openaccessNO
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipOrdu University (BAP) [HD-1614]
dc.description.sponsorshipSeed Fund of Koc University [00006] This study was supported by Ordu University (BAP, HD-1614) and Seed Fund of Koc University (No: 00006). This paper was not funded by EpicentRx, the makers of RRx-001.
dc.description.volume56
dc.identifier.doi10.3233/BIR-190213
dc.identifier.eissn1878-5034
dc.identifier.issn0006-355X
dc.identifier.quartileQ4
dc.identifier.scopus2-s2.0-85077349141
dc.identifier.urihttps://doi.org/10.3233/BIR-190213
dc.identifier.urihttps://hdl.handle.net/20.500.14288/14739
dc.identifier.wos504914800002
dc.keywordsRrx-001
dc.keywordsNitric Oxide
dc.keywordsErythrocyte
dc.keywordsDeformability
dc.keywordsHypoxia Red-Blood-Cells
dc.keywordsS-Nitroso-Glutathione
dc.keywordsPartial-Response
dc.keywordsLung-Cancer
dc.keywordsAgent Rrx-001
dc.keywordsOxide
dc.keywordsDeformability
dc.keywordsNo
dc.keywordsHypoxia
dc.keywordsGlucose-6-Phosphate-Dehydrogenase
dc.language.isoeng
dc.publisherIos Press
dc.relation.ispartofBiorheology
dc.subjectBiophysics
dc.subjectBiomedical engineering
dc.subjectHematology
dc.titleNitrite may serve as a combination partner and a biomarker for the anti-cancer activity of RRx-001
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorUğurel, Elif
local.contributor.kuauthorAksu, Ali Cenk
local.contributor.kuauthorYalçın, Özlem
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1GRADUATE SCHOOL OF HEALTH SCIENCES
local.publication.orgunit2School of Medicine
local.publication.orgunit2Graduate School of Health Sciences
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