Vitamin C has been suggested to play a beneficial role in the prevention and treatment of cancer. However, its in vivo efficacy against cancer is inconsistent even at very high doses. We hypothesized that a high concentration of iron may reduce or eliminate the effectiveness of vitamin C cytotoxicity towards cancer cells. Molt-4 (human leukemia) cells and normal human leukocytes were incubated with holotransferrin (0, 1.25, 2.5, or 5 mg/mL) for an hour. Cells were then treated with sodium ascorbate (0, 64, 128, or 256 µM) and live cells were counted after various times of incubation. At concentrations of 256 µM and 128 µM, ascorbate alone killed all Molt-4 cells in 48 hr and 72 hr, respectively (p<0.001, compared to untreated control), without significantly affecting leukocytes (p>0.05). Preincubation with holotransferrin significantly inhibited the cyto-toxicity of ascorbate toward Molt-4 cells. High concentrations of iron may be responsible for the reduced efficacy of vitamin C in killing leukemia cells and may explain the contradictory results obtained from clinical studies.
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