The Beneficial Effects of Nutritional Compounds on Breast Cancer Metastasis

Abstract

Metastasis, a process of cell migration from an existing cancer site to other anatomical sites, is the leading cause of death among women with breast cancer. There are numerous important signaling mediators that facilitate the migration of tumor cells from the area of origin to outlying tissues. While metastasis may be directed to several tissues, including the brain and the lungs, the primary sight of breast cancer metastasis is the bone (Mundy, 2002; Nguyen et al., 2009). There have been extensive molecular studies in the cancer field that have resulted in a rich array of molecules that contribute to the process of metastasis. A summary of the process with some key metastatic factors may be seen in figure 1. Different proteins are required for such activities as cell migration, adhesion, angiogenesis, and extracellular matrix (ECM) degradation that allows invasion into the surrounding tissues and establishment of new tumors. Additionally, some proteins, such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) contribute to metastasis by helping the cells to sustain themselves independently through angiogenesis once they have migrated to the target tissues (Brown et al., 1995; Kolch et al., 1995; Perrotte et al., 1999; Toi et al., 1995). There have been numerous reports of nutritional compounds that show promise against metastasis. The advantages of using nutritional compounds to treat breast cancer include the lack of adverse side effects and the significantly reduced expense, compared to synthetic drugs. For example, the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are the primary fatty acids found in fish oil. Clinical and epidemiological studies have shown beneficial effects of DHA and EPA on a variety of diseases, including cancer and atherosclerosis (Altenburg & Siddiqui, 2010; Bang & Dyerberg, 1972; Blanckaert et al., 2010; Connolly et al., 1999; Wu et al., 2005). It is also important to note that many drugs used in the treatment of cancer and other diseases were originally discovered as components of nutritional compounds that were further improved upon through isolation of the active compound and modification of the original compound to develop more potent treatments. The purpose of this review is to examine and update the progress of nutritional compounds and their effects on breast cancer metastasis. We will also review the various mechanisms involved in metastasis and how the reported nutritional compounds affect these mechanisms. While this review will focus on key factors that are both important for metastasis and are regarded as targets for most bioactive nutritional