An investigation into the anti-tumour properties and underlying mechanisms of natural polyphenols against ovarian cancer.
Thesis DisciplineCellular and Molecular Biology
Degree GrantorUniversity of Canterbury
Degree NameMaster of Science
Ovarian cancer is the deadliest gynaecologic cancer in New Zealand. Its high mortality rate is due to the fact that it is usually diagnosed at an advanced stage. Advanced ovarian cancer is less responsive to current cytotoxic treatment. Thus, there is an urgent need for novel anti-cancer drugs that can improve patient longevity and quality of life. One of the clinical features of advanced ovarian cancer is the growth of secondary tumours due to the highly metastatic nature of the disease. Cancer cells disseminate from the ovary, some form cell clusters that travel through the abdominal cavity by physiological movement of body fluid and then deposit on the abdominal wall and internal organs to generate secondary tumours. The exact mechanisms of how these cells metastasize are unclear, but prognosis typically worsens if levels of vascular endothelial growth factor (VEGF) are elevated. This study investigated the anti-tumour activities of naturally occurring food compounds resveratrol, acetyl resveratrol and (-)-Epicatechin-3-gallate (EGCG), in cell spheroids/clusters of ovarian cancer. It also examined the protein expression of various proteins involved in the NF-κB signalling pathway. This pathway has been suggested to mediate the secretion of VEGF and is a possible target for the naturally occurring compounds. Results show that resveratrol and acetyl resveratrol reduce cell growth and cellular metabolism in a dose-, time- and cell line- dependent fashion. In addition, the reduction of VEGF is also dose-, time- and cell line- dependent. Paradoxically, another angiogenic protein interleukin-8 (IL-8) secretion is increased. Resveratrol and acetyl resveratrol attenuate the expression of NF-κB but this effect is cell line specific. EGCG has limited effect on cell growth, cellular metabolism and the secretion of VEGF and IL-8. These findings suggest that resveratrol and its derivative may have the ability to supress the angiogenic activity of ovarian cancer cells and warrant further in vivo study.