Reciprocal effects of ascorbate on cancer cell growth and the expression of matrix metalloproteinases and transforming growth factor-beta.

Cancer is associated with increased cell growth, and expression of matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-beta). The dose-dependent effects of ascorbate (Vitamin C) on cancer cell growth, and expression of MMPs and TGF-beta were examined. Renal-adenocarcinoma, melanoma and mammary cancer cells were dosed with 0-100mM ascorbate and examined for cell survival or proliferation, and expression of MMP-1, MMP-2 and TGF-beta at protein and/or mRNA levels. The lower concentrations of ascorbate significantly inhibited cancer cell viability while stimulating MMPs and TGF-beta expression, indicating elimination of cancer cells with damage to the extracellular matrix (ECM). Conversely, ascorbate at higher concentrations dramatically stimulated cell proliferation and inhibited MMPs and TGF-beta expression, implicating growth and ECM advantage.