Antiproliferative Activity of Apples Is Not Due to Phenolic-Induced Hydrogen Peroxide Formation

J Agric Food Chem. 2003 Mar 12;51(6):1718-23. doi: 10.1021/jf026162r.


Anticancer compound screening of natural products using tumor cell lines has been commonly used to identify anticancer drugs. Two highly significant anticancer drugs, paclitaxel (Taxol) and camptothecin, were discovered using tumor cell lines by the U.S. National Cancer Institute (NCI) screening program of plants. It has been recently reported that the inhibition of cancer cell proliferation by fruit extracts was indirectly caused by phenolic-induced H(2)O(2) production in the cell culture media, suggesting that many previously reported effects of flavonoids and phenolic compounds on cultured cells might be from an artifact of H(2)O(2)-induced oxidative stress. The objective of the present study was to determine if apple extracts induced H(2)O(2) formation in common cell culture media and to investigate if the antiproliferative activity of apple extracts was due to phenolic-induced H(2)O(2) formation. It is reported here that apple extracts did not induce H(2)O(2) formation in WME, DMEM, or DMEM/Ham F12 media with the cell culture conditions tested. These same extracts inhibited proliferation of HepG(2) and Caco-2 cells. Therefore, antiproliferative activity of apple extracts was not due to the phenolic-induced H(2)O(2) production in cell culture media. In addition, H(2)O(2) added to the culture medium at 100 microM did not cause inhibition of cell proliferation in either HepG(2) liver cancer cells or Caco-2 colon cancer cells in vitro.

MeSH terms

  • Caco-2 Cells
  • Cell Division / drug effects*
  • Colonic Neoplasms / pathology
  • Culture Media
  • Fruit / chemistry*
  • Humans
  • Hydrogen Peroxide / chemistry*
  • Hydrogen Peroxide / pharmacology
  • Liver Neoplasms / pathology
  • Malus / chemistry*
  • Oxidative Stress
  • Phenols / pharmacology*
  • Plant Extracts / pharmacology
  • Tumor Cells, Cultured


  • Culture Media
  • Phenols
  • Plant Extracts
  • Hydrogen Peroxide