Breast Cancer Inhibition by Grape Constituents

109 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.There has been considerable interest in identifying specific foods and phytochemicals that may have breast cancer preventive properties. Concord grapes are rich in polyphenolic chemicals and anthocyanin pigments that may have biological properties which could suppress cancer such as having antioxidant, antiproliferative, and proapoptotic actions. To determine the potential breast cancer protective action of purple grape juice, we examined the effect of grape juice consumption on the initiation stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis and on the in vivo formation of rat mammary DNA adducts in female Sprague-Dawley rats. We found that specific constituents or combinations of phytochemicals in purple grape juice can block the initiation stage of DMBA-induced rat mammary tumorigenesis. This tumor inhibitory effect was associated with a suppression of mammary DMBA-DNA adduct formation, which in part may be explained by increased liver activity of the phase II metabolizing enzyme, glutathione S-transferase. Based on in vivo research, we evaluated grape color extract (GCE) and two select anthocyanins for their capacity to inhibit benzo[a]pyrene (BP)-induced DNA adduct formation in MCF-10F cells. GCE and each anthocyanins significantly inhibited BP-DNA adduct formation through modulating activities of both bioactivation enzyme, cytochrome P-450 (CYP1A), and detoxification enzymes such as glutathione S-transferase (GST) and quinone reductase (QR). These grape components also suppressed reactive oxygen species (ROS) formation. The constituents did not induce antioxidant response element (ARE)-dependent transcription. These data indicate that grape polyphenols have breast cancer chemopreventive potential due to their capacity to block carcinogen-DNA adduct formation at the initiation stage.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD