Abstract/Summary

Breast cancer is a leading cause of cancer related mortality globally, and epidemiological studies suggest a link between healthy nutrition and cancer prevention. Members of the Brassicaceae family, including watercress, have been extensively studied for their anti-cancer and anti-genotoxic potential. Watercress has a complex phytonutrient profile characterised by high levels of carotenoids, flavonols and glucosinolates Extracts of watercress exhibit strong antioxidant capacity in vitro. Watercress and its components have been associated with the inhibition of the three stages of carcinogenesis: initiation, proliferation and metastasis in in vitro cancer cell models. Phenethyl isothiocyanate (PEITC) is a glucosinolate break-down product and watercress is the richest dietary source of it. It has received considerable attention for its anti-cancer properties and has been tested in a number of clinical trials. In this thesis, the effects of crude watercress extract and PEITC on the metabolic and phenotypic responses in breast cancer and healthy breast tissue cell lines were examined. Radiotherapy is the most common treatment modality for breast cancer patients, it functions by killing cancer cells but it simultaneously damages healthy tissues. We set out to examine synergistic responses to irradiation and watercress/ or PEITC exposures in breast cancer cells and we further investigated whether watercress or PEITC can be protective against radiation induced collateral damage. Watercress and PEITC effectively modulated important cancer cell metabolic pathways associated with anti-cancer endpoints such as cell cycle arrest and DNA damage. In this thesis, PEITC has been shown to enhance the sensitivity of cancer cells to irradiation making the cancer killing process more effective, whereas watercress can protect healthy breast cells from radiation induced damage. These observations appear to be mediated by the ability of PEITC and other phytochemicals in watercress to interact with the antioxidant glutathione. The results obtained from this work remain to be validated in a clinical setting.