Antiproliferative activity of apples is not due to phenolic-induced hydrogen peroxide formation

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 H2O2 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 H2O2-induced oxidative stress. The objective of the present study was to determine if apple extracts induced H2O2 formation in common cell culture media and to investigate if the antiproliferative activity of apple extracts was due to phenolic-induced H2O2 formation. It is reported here that apple extracts did not induce H2O2 formation in WME, DMEM, or DMEM/Ham F-12 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 H2O2 production in cell culture media. In addition, H2O2 added to the culture medium at 100 muM did not cause inhibition of cell proliferation in either HepG2 liver cancer cells or Caco-2 colon cancer cells in vitro.