Apple Phytochemical Extracts Inhibit Proliferation of Estrogen-dependent and Estrogen-independent Human Breast Cancer Cells Through Cell Cycle Modulation

Breast cancer is the most commonly diagnosed cancer in women in the United States. Dietary modification, particularly increased intake of fruits and vegetables, has been consistently associated with a reduced risk of various cancers, including breast cancer. Apples are a major source of dietary phytochemicals and flavonoids and possess potent antioxidant activity and antiproliferative activity in vitro. However, the molecular mechanisms of the anticancer properties of apple phytochemical extracts are not completely understood. In this study a possible mechanism by which apple extracts could inhibit cancer cell growth in vitro using estrogen-dependent MCF-7 and estrogen-independent MDA-MB-231 human breast cancer cell lines was analyzed. The data showed that apple phytochemical extracts significantly inhibited human breast cancer MCF-7 and MDA-MB-231 cell proliferation at concentrations of 10-80 mg/mL (p < 0.05). DNA flow cytometric analysis showed that apple extracts significantly induced G1 arrest in MCF-7 cells in a dose-dependent manner at concentrations >20 mg/mL (p < 0.05). At concentrations of 15, 30, and 50 mg/mL, apple extracts caused a greater increase in the G1/S ratio in MDA-MB-231 cells when compared with MCF-7 cells (p < 0.05). Cyclin D1 and Cdk4 proteins, the two major G1/S transit regulators, decreased in a dose-dependent manner after exposure to apple extracts. These results suggest that the antiproliferative activities of apple phytochemical extracts toward human breast cancer cells might be due to the modulation effects on cell cycle machinery.