Date of Award
Master of Arts (MA)
Breast cancer is a cellular disease characterized by the exploitation of several cellular and molecular mechanisms involved in cell proliferation, apoptosis, motility, and invasion. Effective treatment is available for non-invasive breast cancer at diagnosis, leading to a very high survival rate compared to the low survival rate for those where the breast cancer has spread. Thus, identifying effective therapies and preventative agents is imperative to successfully treat breast cancer. Since diet compromises a large component of the risk factors for breast cancer, it would be beneficial to examine dietary compounds that could potentially play a beneficial role in inhibiting cancer progression. For this thesis the two dietary compounds chosen for investigation are resveratrol and genistein. Both of these compounds can be naturally found within the diet. Resveratrol is present within the skin of red grapes and genistein is commonly found in soy products. Preliminary studies reveal that these agents have a cancer fighting potential at the level of invasion, proliferation, apoptosis, angiogenesis and motility, steps of the complex process of metastasis.
Since current therapies are ineffective in treating the most advanced form of breast cancer, examining dietary agents and their potential role in inhibition of breast cancer may provide valuable insight on the influence of diet in inhibiting cancer progression. Our research aims to investigate the use of two dietary agents (resveratrol and genistein) to effectively combat metastasis at multiple targets simultaneously. The hypothesis for this research is that the combination of two different dietary compounds (genistein and resveratrol) could lead to a greater success in treating breast cancer invasion and metastasis by targeting multiple steps in metastasis. This thesis aims at identifying where these agents overlap in their mechanism of action and differ in their exploitation of pathways in metastasis. This finding could lead to a combinatory therapy to treat and prevent metastasized breast cancer via dietary agents.
From an extensive review of research literature in this thesis, resveratrol may play a significant role in preventing/treating breast cancer by decreasing the invasive phenotype of cancer cells, altering MMP expression, adhesion and migration of the cancer cells. In addition, resveratrol also decreases cell proliferation, apoptosis and effectively represses angiogenesis. These findings suggest that resveratrol exploits multiple signaling pathways involved in cancer progression to effectively combat cancer.
From an extensive review of research literature on genistein revealed that it effectively reduces metastasis through a wide variety of mechanisms. Genistein decreases invasion of cancer cells by inhibiting migration, cell adhesion, proliferation, and played a significant role in modulating the expression of angiogenesis facilitators and angiogenesis inhibitors.
This thesis identifies the similar and different targets in breast cancer progression that are utilized by both resveratrol and genistein to inhibit metastasis. These include: inhibition of MMPs for invasion, adhesion and migration of cancer cells, angiogenesis, cell cycle proteins and cell proliferation pathways employed by cancer cells, and an increase in caspase activity and apoptosis (Fig 14a-d).
Thus, the combined effects of genistein and resveratrol should lead to a more substantial increase by inhibiting tangential or multi-layered events in metastasis and would probably have a greater potential preventing and treating metastasized breast cancer at multiple levels.
This thesis also proposes future studies to explore the combinatory effects of resveratrol and genistein in inhibiting breast cancer progression at the cellular level.
Wolfe, Brittany, "Roles of Resveratrol and Genistein in Invasion and Metastasis of Breast Cancer" (2012). College of Science and Health Theses and Dissertations. 5.