In this study we used standard cell culture techniques using three prostate cancer cell lines DU145, LNCaP and PC3. Green tea extract (EGCG) alone induced apoptosis in the three cell lines in a dose-dependent manner. DHT stimulated growth in LNCaP cells, but the presence of DHT, sensitised these cells to apoptosis induced by EGCG or an IGF-I receptor inhibitor (AG1024). We also found that EGCG via its antioxidant action negated the efficacy of radiotherapy through the induction of superoxide dismutase enzymes. Among the three ECM used, fibronectin but not laminin or vitronectin activated a survival pathway that protected DU145 but not LNCaP prostate cancer cells against ceramide and Docetaxel-induced apoptosis but not that induced by radiotherapy. This survival effect involved the insulin-like growth factor (IGF-I) and β1 integrin receptors and was associated with an increase in the recruitment of the β1 integrin receptor to a complex containing the IGF-IR and protein receptor for activated C kinase (RACK-1) and an increase in the abundance of a MAPK-phosphatase, MKP-1. Our study has shown that EGCG can act as a chemopreventive agent in presence of androgen but it may not provide any additive effect in prostate cancer treated with antiandrogens. In addition we concluded that drinking green tea prior to radiotherapy treatment could reduce its efficacy. We have also shown that the susceptibility to chemotherapy might be improved by targeting either the IGF-I or β1 integrin receptors.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:520246 |
| Date | January 2010 |
| Creators | Thomas, Francis |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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