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

Cancer Lett. 2007 Oct 18;256(1):49-55. doi: 10.1016/j.canlet.2007.05.009. Epub 2007 Jun 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Survival / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Melanoma / metabolism
  • RNA, Messenger / metabolism
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism

Substances

  • Antioxidants
  • RNA, Messenger
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1
  • Ascorbic Acid