ASCORBATE ON CELL-GROWTH AND DIFFERENTIATION

Ascorbate, an essential nutrient in humans, primates, and guinea pig, is involved in many cellular functions. Ascorbate also modulates cell growth and differentiation. Ascorbate can reduce or stimulate the growth of tumor cells, depending on the cell type. The inhibitory effect is not specific for the biological active isomer L-ascorbate, and isoascorbate and D-ascorbate are more effective in reducing cell growth than L-ascorbate. These results indicate that ascorbate has a cytotoxic effect by killing cells directly, rather a cytostatic one. However, only L-ascorbate is able to stimulate cell growth, but the mechanism of this stimulation is still unknown. L-Ascorbate stimulates the in vitro differentiation of several mesenchyme-derived cell types by altering the expression of multiple genes as the cell progresses through specific differentiation programs. Stimulation of collagen matrix at gene transcription, mRNA stabilization, hydroxylation, and secretion is a key role for L-ascorbate. L-Ascorbate also prevents cell transformation by stabilization of the differentiated state and cooperates with other agents to induce differentiation in a leukemia cell line.