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Ibrahim Malami

Ibrahim Malami

Usmanu Danfodiyo University, Nigeria

Title: Identification of uridine-cytidine kinase 2 inhibitors from the rhizome of Alpinia mutica Roxb. against colorectal cancer, HT-29 cells

Biography

Biography: Ibrahim Malami

Abstract

Uridine-cytidine kinase 2 is an enzyme that is overexpressed in abnormal cell growth and therefore, implicated in all types of cancers. Due to the selective expression of UCK2 in cancer cells, a selective inhibition of this key enzyme necessitates the discovery of its potential inhibitors for cancer chemotherapy. The present study was carried out to demonstrate the potentials of natural phytochemicals in inhibiting UCK2 enzyme activity useful for colorectal cancer therapy. Flavokawain B and alpinetin were isolated from the the rhizome of Alpinia mutica. These compounds were found to inhibit 50% cell proliferation at low IC50 concentrations. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity using in vitro kinase assay. UCK2 was substantially downregulated in treated HT-29 cells both at gene and protein level. Subsequently, downregulation of 18S ribosomal RNA biosynthesis was confirmed using live cell fluorescence imaging. This study further suggested the possibility of p53 activation through MDM2 downregulation mediated by UCK2 enzyme inhibition. The expression of p53 protein induced p53 transactivation of targets genes that are essential in triggering cell cycle arrest and apoptosis of HT-29 cells. In this respect, apoptosis induction was further confirmed using DNA fragmentation analysis. Results from the in vitro studies have shown the ability of flavokawain B and alpinetin to target UCK2 enzyme specifically, inducing cell cycle arrest and subsequently leading to cancer cell death, possibly through interfering the MDM2-p53 signaling pathway. These phenomena have proven that the bioactive compounds could be useful for future therapeutic use in colorectal cancer.