Anti-cancer activities of Vaccinium macrocarpon: Apoptosis induction and matrix metalloproteinase inhibition

Increasingly, dietary intervention is being used as a means of preventing the onset or delaying the development of cancer. Targets of such intervention often include cell death pathways and the mechanisms responsible for cancer invasion and metastasis. Previously, research has identified the North American Cranberry's (Vaccinium macrocarpon) apoptosis-inducing and invasion-limiting activities in a variety of tumour cell lines, though little work has been conducted to determine the mechanisms responsible for these anticancer activities. The work presented in this thesis serves to elucidate some of those mechanisms by evaluating the effects of cranberry phytochemicals on DU145 human prostate adenocarcinoma and MDAMB-231 human breast carcinoma cells. Briefly, it was found that treating DU145 cells with cranberry extracts induces apoptotic cell death through caspase-8-mediated cleavage of Bid to truncated Bid, resulting in the release of apoptogenic factors from the mitochondria and the subsequent activation of caspase-9—ultimately resulting in PARP inhibition and an increase in cytoplasmic nucleosome enrichment (hallmarks of apoptosis). Furthermore, cranberry has also been observed to directly inhibit the gelatinolytic activity of matrix metalloproteinases as well as impairing their secretion from DU145 and MDA-MB-231 cells. This study has thus elucidated some of the mechanisms responsible for cranberry's induction of programmed cell death and inhibition of MMP activity, and has thus established the potential value of cranberry phytochemicals in the development of novel chemopreventative strategies.