Jaksevicius, Andrius (2017) Elucidation of mechanisms by which culinary herbs and spices exert their inhibitory action on the growth of CRC cells in vitro. (PhD thesis), Kingston University, .
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer in the developed countries and the incidence is rising in the developing regions. Chronic inflammation, which is propagated by overexpression of cyclooxygenase-2 (COX-2) and its major product prostaglandin E2 (PGE2), plays a key role in the development of CRC. Culinary herbs and spices (CHS) are rich in polyphenols, have a high anti-oxidant capacity and possess anti-inflammatory activity. It has been shown that CHS inhibit the growth of CRC cells, however, their anti-carcinogenic mechanisms are mainly unknown. Hence, the aim of this study was to identify the CHS that were most potent inhibiting the growth of CRC cells, and subsequently to elucidate their anti-carcinogenic mechanisms, in particular, focusing on COX-2, the Wnt/β-catenin signalling pathway, and proteins involved in apoptosis. Another goal was to investigate whether combining the CHS would result in synergistic effects on the above. This study demonstrated that CHS extracted in water/or ethanol and their combinations inhibited CRC cell growth. This study also revealed that the most potent CHS extracted in ethanol (turmeric (TE), bay leaf (BLE) and ginger (GE)) and combinations downregulated the expression of COX-2 and suppressed COX-2 activity by reducing PGE2 release; their effect was comparable to that of the selective COX-2 inhibitor Celecoxib (50 μM). These CHS also induced apoptosis in CRC cells by targeting several key proteins: p53, caspase-3, and PAPR. However, the CHS did not have an effect on Wnt signalling pathway, which partially could be due to insufficient treatment time. In conclusion, this study demonstrated that CHS and their combinations inhibited CRC cell growth, inhibited COX-2 expression and activity, and modulated several key molecules involved in the development of CRC. Based on these findings, CHS have the potential to be utilized for CRC chemoprevention and possibly be used as a complimentary treatment. However, in vivo studies are needed to establish the true potential of these foods.
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