Journal
ANTICANCER RESEARCH
Volume 36, Issue 11, Pages 5965-5973Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.11184
Keywords
Glycoside; cholangiocarcinoma; cell growth; G(0)/G(1) arrest; cell apoptosis
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Funding
- TRF Senior Research Grant
- Thailand Research Fund
- Khon Kaen University [TRF5780012, KKU562601]
- National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster [SHeP-GMS-PD55210]
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Background/Aim: The treatment of cholangio-carcinoma (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 G(0)/G(1) 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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