Novel Synthetic Mono-triazole Glycosides Induce G0/G1 Cell-cycle Arrest and Apoptosis in Cholangiocarcinoma Cells.

BACKGROUND/AIM The treatment of cholangiocarcinoma (CCA) is still ineffective and the search for a novel treatment is needed. In this study, eight novel mono-triazole glycosides (W1-W8) were synthesized and tested for their anticancer activities in CCA cell lines. MATERIALS AND METHODS The anti-proliferation effect and the underlying mechanisms of the triazole glycosides were explored. Viable cells were determined using the MTT test. RESULTS Among glycosides tested, W4 and W5 exhibited the most potent anticancer activity in a dose- and time-dependent fashion. Flow cytometry and wstern blot analysis revealed that W4 and W5 induced G0/G1 phase cell-cycle arrest through down-regulation of cyclin D1, cyclin E and induction of cyclin-dependent kinase inhibitors, p27 and p21 protein expression. Annexin V/propidium iodide (PI) staining demonstrated that W4 and W5 also induced apoptotic cells in a dose-dependent manner via caspase signaling cascade. CONCLUSION Together, these findings imply that the novel synthetic glycosides might be a promising anticancer agent for CCA.

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