Pharmacologic Ascorbate Influences Multiple Cellular Pathways Preferentially in Cancer Cells
Interests have risen in the research into0 using pharmacologic doses of ascorbate for cancer treatment, due to its potential efficacy and low toxicities. It has been revealed that the anticancer activity of ascorbate is primarily attributed to its pro-oxidant effect for hydrogen peroxide (H2O2) generation in the extracellular spaces, which reduces tumor growth and metastasis without causing harm to normal cells. It is of virtual interest why pharmacologic concentrations of ascorbate exhibit this selective cytotoxicity to some cancer cells. Through investigation in its mechanisms of action, it is suggested that pharmacologic ascorbate induces diverse biological responses that differently influence cancer cells versus normal cells. This chapter discusses several mechanisms that lead to preferential cancer cell inhibition, including cancer cell iron metabolism, DNA damage, depletion of cancer cellular energy sources, and inhibition of microtubule dynamics. The multitargeting mechanisms of ascorbate anticancer action are advantageous as high-dose ascorbate has minimal toxicities. The multiple mechanisms open doors for combination treatment with various approved cancer therapies.