An Electrochemical Engineering Perspective of Nitric Oxide in Tumors: Why the Combination of an Allosteric Effector of Hemoglobin with Dietary Sodium Nitrite Should Be Effective in Treating Vascularized Tumors?

Abstract

At high (~10-6 M) concentrations nitric oxide (NO), over-expressed in many tumors, induces apoptosis (controlled suicide of cells), which is of essence in avoiding cell proliferation. The excess NO in vascularized tumors is, however, depleted by out-diffusion to blood, where it S-nitrosates proteins and peptides. The out-diffusion explains the observations of Judah Folkman of the dormancy of tumors until their vascularization and their virulence after vascularization. The export of NO from tumors to blood could be slowed by converting part of the nitrite stored in erythrocytes to NO and nitrate in a reaction catalyzed by deoxyhemoglobin. As shown by Max Perutz, oxyhemoglobin is converted to deoxyhemoglobin upon binding an allosteric effector, such as inositol hexaphosphate, bezafibrate or efaproxiral. Local administration the effector, in combination with dietary intake of NaNO2, should raise the tumor-passing blood NO concentration, reduce the tumor to blood NO flux and increase the likelihood of apoptosis.