Publication: Induction of apoptosis in cholangiocarcinoma by an andrographolide analogue is mediated through topoisomerase II alpha inhibition
Issued Date
2014-01-15
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ISSN
18790712
00142999
00142999
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2-s2.0-84891545203
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Mahidol University
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SCOPUS
Bibliographic Citation
European Journal of Pharmacology. Vol.723, No.1 (2014), 148-155
Suggested Citation
Jintapat Nateewattana, Suman Dutta, Somrudee Reabroi, Rungnapha Saeeng, Sakkasem Kasemsook, Arthit Chairoungdua, Jittima Weerachayaphorn, Sopit Wongkham, Pawinee Piyachaturawat Induction of apoptosis in cholangiocarcinoma by an andrographolide analogue is mediated through topoisomerase II alpha inhibition. European Journal of Pharmacology. Vol.723, No.1 (2014), 148-155. doi:10.1016/j.ejphar.2013.12.002 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34908
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Title
Induction of apoptosis in cholangiocarcinoma by an andrographolide analogue is mediated through topoisomerase II alpha inhibition
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Abstract
Cholangiocarcinoma (CCA), the common primary malignant tumor of bile duct epithelial cells, is unresponsive to most chemotherapeutic drugs. Diagnosis with CCA has a poor prognosis, and therefore urgently requires effective therapeutic agents. In the present study we investigated anti-cancer effects of andrographolide analogue 3A.1 (19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide) and its mechanism in human CCA cell line KKU-M213 derived from a Thai CCA patient. By 24 h after exposure, the analogue 3A.1 exhibited a potent cytotoxic effect on KKU-M213 cells with an inhibition concentration 50 (IC50) of approximately 8.0 μM. Analogue 3A.1 suppressed DNA topoisomerase II α (Topo II α) protein expression, arrested the cell cycle at sub G0/G1 phase, induced cleavage of DNA repair protein poly (ADP-ribose) polymerases-1 (PARP-1), and enhanced expression of tumor suppressor protein p53 and pro-apoptotic protein Bax. In addition, analogue 3A.1 induced caspase 3 activity and inhibited cyclin D1, CDK6, and COX-2 protein expression. These results suggest that andrographolide analogue 3A.1, a novel topo II inhibitor, has significant potential to be developed as a new anticancer agent for the treatment of CCA. © 2013 Elsevier B.V.