title: In vitro and in vivo antitumor activity of tiliacorinine in human cholangiocarcinoma.
abstract: Cholangiocarcinoma (CCA) is a fatal cancer with poor prognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in unfavorable outcomes. At present, plant-derived compounds are gaining interest as potential cancer therapeutics, particularly for treatment-refractory cancers. In this study, antitumor activity of tiliacorinine, the major alkaloid isolated from a tropical plant, on CCA was first demonstrated. Antiproliferative effects of tiliacorinine on human CCA cell lines were investigated using SRB assays. Acridine orange/ethidium bromide staining, flow cytometric analysis and DNA laddering assays were used for apoptotic determination. Apoptosis-related proteins were verified by Western blotting and antitumor activity of tiliacorinine in vivo was demonstrated in CCA xenografted mice. Tiliacorinine significantly inhibited proliferation of human CCA cell lines with IC50 4.5-7 μM by inducing apoptosis through caspase activation, up- regulation of BAX, and down-regulation of BclxL and XIAP. Tiliacorinine considerably reduced tumor growth in CCA xenografted mice. These results demonstrated antitumor effects of tiliacorinine on human CCA in vitro and in vivo. Tiliacorinine may be an effective agent for CCA treatment.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand E-mail : sopit@kku.ac.th.
authors.forename: Somkid
authors.initials: S
authors.lastname: Janeklang
authors.forename: Archawin
authors.initials: A
authors.lastname: Nakaew
authors.forename: Kulthida
authors.initials: K
authors.lastname: Vaeteewoottacharn
authors.forename: Wunchana
authors.initials: W
authors.lastname: Seubwai
authors.forename: Patcharee
authors.initials: P
authors.lastname: Boonsiri
authors.forename: Gorkem
authors.initials: G
authors.lastname: Kismali
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D001650:Bile Duct Neoplasms; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018281:Cholangiocarcinoma; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D044182:Benzylisoquinolines; D010936:Plant Extracts; C000598346:tiliacorinine; D020169:Caspases