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

Selma Cirrik1, Elif Ugurel2, Ali Cenk Aksu2

  • 1Ordu University, Faculty of Medicine, Department of Physiology, Ordu, Turkey.

Biorheology
|October 24, 2019
PubMed
Abstract

Insights

RRx-001, an anti-cancer immunotherapeutic, can alter red blood cell deformability. Combining RRx-001 with nitrite under hypoxia significantly enhances erythrocyte deformability by increasing nitric oxide production.

Area of Science:

  • Oncology
  • Immunotherapy
  • Hematology

Background:

  • RRx-001 is an anti-cancer immunotherapeutic agent.
  • It enhances tumor sensitivity to chemotherapy through hemoglobin binding and nitrite reductase activity.
  • The study investigates RRx-001's impact on red blood cell (RBC) function.

Purpose of the Study:

  • To examine the effect of RRx-001 on erythrocyte deformability at clinically relevant doses.
  • To assess the role of nitric oxide (NO) in mediating these effects.
  • To explore potential therapeutic strategies involving RRx-001 and nitrite.

Main Methods:

  • Erythrocyte deformability was measured using ektacytometry under normoxic and hypoxic conditions.
  • RRx-001 was tested at various concentrations (1-1000 micro molar).
  • Intracellular NO levels were quantified using DAF-FM-DA, and effects of ODQ and L-NAME were assessed.

Main Results:

  • Higher doses of RRx-001 (100, 1000 micro molar) significantly reduced erythrocyte deformability under hypoxia.
  • Low-dose RRx-001 (20 micro molar) did not alter deformability alone or with ODQ/L-NAME.
  • RRx-001 combined with nitrite significantly increased erythrocyte deformability under hypoxia, correlating with elevated NO production.

Conclusions:

  • Co-administration of RRx-001 and nitrite under hypoxia enhances erythrocyte deformability via increased NO production.
  • Monitoring and supplementing serum nitrite levels in cancer patients treated with RRx-001 may optimize therapeutic efficacy.
  • This suggests a potential adjunctive role for nitrite in RRx-001 cancer immunotherapy.

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