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Antiproliferative activity of apples is not due to phenolic-induced hydrogen peroxide formation
1Department of Food Science and Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, New York 14853-7201, USA. RL23@cornell.edu
Abstract:
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.
Insights
Apple extracts show anticancer properties by inhibiting cancer cell proliferation. This effect is not due to hydrogen peroxide (H2O2) production in cell culture media, as confirmed by experimental results.
Area of Science:
- Natural product chemistry
- Cell biology
- Cancer research
Background:
- Natural products are a common source for anticancer drug discovery, exemplified by paclitaxel (Taxol).
- Recent studies suggest that phenolic compounds in fruit extracts may inhibit cancer cell proliferation indirectly through hydrogen peroxide (H2O2) production, potentially causing artifactual results in cell culture.
- This raises questions about the validity of previously reported antiproliferative effects of flavonoids and phenolics.
Purpose of the Study:
- To investigate whether apple extracts induce H2O2 formation in standard cell culture media.
- To determine if the observed antiproliferative activity of apple extracts on cancer cells is a result of H2O2 production.
- To assess the direct impact of H2O2 on cancer cell proliferation.
Main Methods:
- Apple extracts were tested for their ability to induce H2O2 formation in various cell culture media (WME, DMEM, DMEM/Ham F12).
- The antiproliferative effects of apple extracts were evaluated on HepG2 (liver cancer) and Caco-2 (colon cancer) cell lines.
- H2O2 was directly added to the cell culture medium at a concentration of 100 microM to assess its direct impact on HepG2 and Caco-2 cell proliferation.
Main Results:
- Apple extracts did not induce H2O2 formation under the tested cell culture conditions.
- The same apple extracts demonstrated significant inhibition of proliferation in both HepG2 and Caco-2 cell lines.
- Exogenous H2O2 at 100 microM did not inhibit the proliferation of HepG2 or Caco-2 cells in vitro.
Conclusions:
- The antiproliferative activity of apple extracts against HepG2 and Caco-2 cells is not attributable to H2O2 production in the cell culture media.
- The study provides evidence against H2O2-induced oxidative stress as the mechanism for the observed anticancer effects of apple extracts.
- These findings suggest that apple extracts possess genuine antiproliferative properties independent of H2O2 artifacts.