Abstract
The effect of high doses of vitamin C for the treatment of cancer has been controversial. Our previous studies, and studies by others, have reported that vitamin C at concentrations of 0.25–1.0 mM induced a dose- and time-dependent inhibition of proliferation in acute myeloid leukemia (AML) cell lines and in leukemic cells from peripheral blood specimens obtained from patients with AML. Treatment of cells with high doses of vitamin C resulted in an immediate increase in intracellular total glutathione content and glutathione-S transferase activity that was accompanied by the uptake of cysteine. These results suggest a new role for high concentrations of vitamin C in modulation of intracellular sulfur containing compounds, such as glutathione and cysteine. This review, discussing biochemical pharmacologic studies, including pharmacogenomic and pharmacoproteomic studies, presents the different pharmacological effects of vitamin C currently under investigation.
Highlights
There is increasing evidence that vitamin C is selectively toxic to some types of tumor cells, functioning as a pro-oxidant [1,2,3]
Studies have established that the growth of leukemic progenitor cells from patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) can be significantly modulated by vitamin C [6,7]
These results demonstrated that thiol/disulfide exchange proteins are regulated in NB4 cells after vitamin C exposure
Summary
There is increasing evidence that vitamin C (ascorbate) is selectively toxic to some types of tumor cells, functioning as a pro-oxidant [1,2,3]. Physiological concentration of vitamin C is under 0.1 mM, while plasma vitamin C concentrations that cause toxicity to cancer cells in vitro (1 mM–10 mM, depending on cell lines) can be achieved clinically by intravenous administration, which means a high dose of vitamin C. Our previous results indicated that treatment of malignant lymphocytic cell lines with vitamin C (0.25–1 mM) for 24 h led to a marked dose-dependent decrease of cell proliferation [17]. A similar result was obtained with cells containing over 90% of blasts from patients with AML In these cell lines, induction of apoptosis by vitamin C demonstrated a dose-dependent effect. Vitamin C weakly induced apoptosis in ovarian cell lines, including SK-OV-3, OVCAR-3 and 2774 [17]. HL-60, human myeloid leukemia; NB4, NB4-R1, NB4-R2, human acute promyelocytic leukemia (APL); KG1, human myeloblast; K562, human chronic myelogenous leukemia; U937, human histiocytic lymphoma; OVCAR, SK-OV3, ovarian cancer; JLP119, human lymphoma; MCF7, MB231, Hs587t, human breast cancer; KLN205, mouse lung cancer; RAG, mouse kidney cancer; CT26, mouse colon cancer; B16, mouse melanoma; LL/2, mouse lung cancer; Hs587Bst, human normal breast cells; CCD34SK, human normal fibroblast cells. * IC50 value was determined using H3 incorporation proliferation assay for 24 h
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