Fig. 8.

Mn porphyrin redox cycling with ascorbate will cause differential effects in cancer and normal cells. Due to the high cellular levels of ascorbate, it is likely that cationic Mn(III) N-alkylpyridylporphyrins will be reduced with ascorbate to Mn^IIP within the cell, which will then act as a reductant, either reacting with O₂^–· or ONOO^– or ClO^– or H₂O₂ closing the catalytic cycle. Due to the abundance of oxygen relative to the levels of other species, Mn^IIP may prefer reducing O₂ to O₂^–· which will eventually dismute to H₂O₂. The normal cell has the abundance of peroxide-removing enzymes, thus the contribution of Fenton chemistry leading to a deleterious ^–OH radical may be negligible [203,204,205,206,207,208,209,210,211]. Cancer cells are frequently deprived of H₂O₂-removing enzymes, thus excessive amounts of peroxide will be formed. In such a situation, coupling with ascorbate involves O₂ or O₂^–· (catalytic in nature) and may produce pro-oxidative effects, and favor cancer cell death as opposed to normal, nontransformed cells [9,27,148].