Cellular effect of protease inhibitor concentrates from legumes in prostate cancer

Abstract

Prostate cancer is the most prevalent male cancer in the United Kingdom. The etiology of prostate cancer is complex and multifactorial, with diet appearing to play a crucial role in disease prevention. Diets consumed in “Westernized” societies are rich in fats and processed foods, while diets consumed in Asia, where prostate cancer incidence is comparatively lower, are rich in plant based foods. Epidemiological evidence supports the protective role of legumes and pulses, such as soybean, against prostate carcinogenesis. A putative chemo-preventive agent present in soybean and legumes is the Bowman-Birk Inhibitor (BBI), a protease inhibitor whose anti-cancer potential has been demonstrated in in vitro and in vivo models , including prostate cancer. The aim of this thesis was to investigate the effects of soybean and chickpea protease inhibitor concentrates (PICs) in LNCaP, DU 145 and PC-3 prostate cancer cell models that represented differing stages of carcinogenesis, namely initiation, promotion and metastasis. A pilot in vivo study was also carried out in mice injected with DU 145 cells to investigate the effect on tumour mass growth. Our study highlights anti-genotoxic activity of chickpea PIC that induced a reduction in H2O2-induced DNA strand breaks assessed by the Comet assay in LNCaP cells. Both PICs proved effective against cancer promotion, decreasing cell proliferation in all three cell lines in vitro, with cell-cycle arrest apparent at the S phase in PC-3 cells The findings suggest that soybean PIC may possess anti-metastatic activity given the observed inhibition of highly invasive PC-3 cells through Matrigel and associated down-regulation of MMP-1. A beneficial modulation of genes linked to the initiation, promotion and progression stages of prostate carcinogenesis was observed. In conclusion, our study supports the role of PICs as anti-cancer agents against prostate cancer and suggests possible mechanisms of actions accounting for the observed effects.

Date of Award	Jun 2014
Original language	English
Sponsors	Vice Chancellor Research Studentship
Supervisor	Pamela Magee (Supervisor), Chris Gill (Supervisor), Richard Owusu-Apenten (Supervisor) & Ian R. Rowland (Supervisor)