Research suggested high intake of fruits and vegetables is negatively associated with reduced risk of cancer, and their health benefits are attributed to the abundant phytochemicals from fruits and vegetables. However, individual phytochemical alone does not show consistent anti-cancer effects in clinical trials as fruits and vegetables in epidemiological studies. We propose that the health benefits of fruits vegetables are due to the combination of different phytochemicals, which cannot be mimicked by individual compound alone. Apples are a commonly consumed fruit with rich phytochemical content and contribute to 33% of the fruit dietary phenolics consumption. Apples peels contain higher phytochemical content than apple flesh and have been used as a valuable food ingredient to fortify dietary phytochemical consumption. The anti-cancer effects of apples and apple peels have been reported in epidemiological studies, animal studies, as well as in vitro cell culture studies. However, its underlying mechanisms has not been fully understood. Therefore, this study aimed to explore the potential anti-proliferative and anti-metastatic effects of phytochemicals from apple peels as a natural mixture, instead of individual pure compounds. This study demonstrated that apple peel extracts inhibited MDA-MB-231 human breast cancer proliferation and induced cell cycle arrest in a dose-dependent manner. Apple peel extracts achieved antiproliferative effects by regulating cyclin D1 through three different mechanisms. Firstly, apple peel extracts inhibited cyclin D1 transcription via EGFR/ Ras/PI3K/AKT/NF-κB pathway; secondly, apple peel extracts accelerated cyclin D1 degradation via EGFR/Ras/PI3K/Akt/GSK3β pathway; thirdly, apple peel extracts prevented cyclin D1 from activating its partner CDK4 via EGFR/Ras/PI3K/Akt/p21 pathway. Breast cancer, especially triple negative breast cancer has a high tendency of metastasis. The distant recurrences lead to poor prognosis and low survival rate. The objective of the second project is to understand the anti-metastatic effects of apple peel extracts towards human breast cancer cell and its underlying mechanisms. Our results demonstrated that the blockage of JAK/STAT3 pathway suppressed MDA-MB-231 human breast cancer cell migration. Apple peel extracts suppressed MDA-MB-231 cell migration via EGFR/JAK2(3)/STAT3/MMP-2 pathway. Therefore, apple peel has a potential to be used as a natural product for prevention of breast cancer metastasis. Besides the combinations of phytochemicals within apple peels, we also explored the potential combination effects of apple peel extracts and selected bioactive compounds (resveratrol, ursolic acid, and apigenin) in inhibiting human breast cancer cell proliferation in the third project. The result demonstrated that apple peel extracts can interact synergistically with resveratrol and ursolic acid in inhibiting MCF-7 and MDA-MB-231 human breast cancer cell proliferation. These data shed light on understanding the protective activity of apple peel against breast cancer.