Can apple antioxidants inhibit tumor cell proliferation?: Generation of H2O2 during interaction of phenolic compounds with cell culture media

It has recently been suggested that the ability of apple extracts to inhibit proliferation of tumor cells in vitro may be due to phenolic/flavonoid antioxidants. Our study demonstrates that this inhibition is caused indirectly by H2O2 generated through interaction of the phenolics with the cell culture media. The results indicate that many previously reported effects of flavonoids and phenolic compounds on cultured cells may result from similar artifactual generation of oxidative stress. We suggest that in order to prevent such artifacts, the use of catalase and/or metmyoglobin in the presence of reducing agents should be considered as a method to decompose H2O2 and prevent generation of other reactive oxygen species, which could affect cell proliferation. The use of tumor cells and nontumor cells in a bioassay to measure antioxidant activity, in this context, is potentially misleading and should be applied with caution.