Date of Award

5-2012

Document Type

Honors Thesis

Degree Name

Bachelor of Science

Department

Biological Science

Advisor/Committee Chair

J. Andres Melendez

Abstract

Throughout your lifetime renewable tissues and those which are exposed to prolonged inflammation experience an accumulation of senescent cells. These cells have previously been shown to acquire the senescence-associated secretory phenotype (SASP) that promotes proliferation and tumorigenesis of epithelial cells, thus increasing the invasive ability of tumor cells (1). SASP is characterized by an upregulation in mRNA levels of a number of secretory factors, such as growth factors, cytokines, and chemokines. It has been shown that lifetime exposure to oxidative stress can influence cell cytoskeleton reorganization and influence aging processes (2). In addition matrix metalloproteinases are key SASP factors that degrade the extracellular matrix (ECM), accompanying the aging process and are in part regulated by the production of reactive oxygen species (ROS) (2). We sought to first determine if SASP factors modulate the invasive properties of tumor cells as previously reported and if this process is redox-dependent. In addition, we questioned whether efficient antioxidant compounds, such as apple peel extract (APE) derived from Gala apples, that have been previously shown to contain several classes of polyphenolic antioxidants could modulate invasion and SASP. We have shown that both the invasive and migratory properties of metastatic mammary tumor cells (MDAMB231) can be prevented by treatment with the nutritional antioxidant, APE. Furthermore, we have established that the SASP-dependent regulation of tumor migration and invasion is impaired by treatment with APE. Overall, by gaining an understanding of the SASP by manipulating tumor invasion and also identifying key factors that are upregulated, future studies may reveal the interplay of molecular mechanisms of SASP, with the long-term goal of finding natural or synthetic therapies that can control the deleterious effects of this phenotype.

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