AI Article Synopsis
- RRx-001 is an anti-cancer drug that enhances drug sensitivity in resistant tumors by binding to hemoglobin and boosting nitrite activity.
- The study investigated how different doses of RRx-001 affect the flexibility of red blood cells (erythrocytes) under low oxygen conditions (hypoxia).
- Results showed that higher doses decreased deformability, while a lower dose combined with nitrite increased it, suggesting that measuring and potentially supplementing serum nitrite levels in cancer patients treated with RRx-001 could enhance treatment efficacy.
Article Abstract
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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| http://dx.doi.org/10.3233/BIR-190213 | DOI Listing |
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