Nitrite may serve as a combination partner and a biomarker for the anti-cancer activity of RRx-001.
Biorheology
; 56(4): 221-235, 2019.
Article
em En
| MEDLINE
| ID: mdl-31640080
BACKGROUND: 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.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Azetidinas
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Neoplasias
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Antineoplásicos
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Óxido Nítrico
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Nitritos
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Nitrocompostos
Limite:
Humans
Idioma:
En
Revista:
Biorheology
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Turquia