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In vitro and In vivo Antitumor Activity of Tiliacorinine in Human Cholangiocarcinoma

  • Janeklang, Somkid (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Nakaew, Archawin (Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University) ;
  • Vaeteewoottacharn, Kulthida (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Seubwai, Wunchana (Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University) ;
  • Boonsiri, Patcharee (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Kismali, Gorkem (Department of Biochemistry, Faculty of Veterinary Medicine, Ankara University) ;
  • Suksamrarn, Apichart (Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University) ;
  • Okada, Seiji (Division of Hematopoiesis, Center of AIDS Research, Kumamoto University) ;
  • Wongkham, Sopit (Department of Biochemistry, Faculty of Medicine, Khon Kaen University)
  • Published : 2014.09.15

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 $IC_{50}$ $4.5-7{\mu}M$ by inducing apoptosis through caspase activation, upregulation of BAX, and downregulation of $Bcl_{xL}$ 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.

Keywords

Antitumor activity;apoptosis;growth inhibition;bile duct cancer;alkaloid

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