title: Cepharanthine exerts antitumor activity on cholangiocarcinoma by inhibiting NF-kappaB.
abstract: Cholangiocarcinoma (CCA) is a major cause of cancer deaths in northeast Thailand. It is aggressive, highly metastatic, and responds poorly to traditional chemotherapy. We demonstrated the potential for Cepharanthine (CEP), a biscoclaurine alkaloid extracted from Stephania cepharantha, to treat CCA. CEP significantly inhibited growth of human CCA cell lines in a dose- and time-dependent manner, regardless of the histologic type of tumor origin. Increasing cell apoptosis via caspase-3 and capase-9 activation was demonstrated in CEP-treated cells. We found that CEP controlled the growth of CCA cells through nuclear factor-kappa B (NF-kappaB) inactivation by inhibiting nuclear translocation. CEP treatment effectively reduced tumor size in CCA-inoculated mice without serious side effects. CEP also increased cell apoptosis in primary histocultures of CCA patients' tissues; this was demonstrated by immunohistochemistry using TUNEL staining. Our results suggest that CEP possesses therapeutic potential against human CCA.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Wunchana
authors.initials: W
authors.lastname: Seubwai
authors.forename: Kulthida
authors.initials: K
authors.lastname: Vaeteewoottacharn
authors.forename: Masateru
authors.initials: M
authors.lastname: Hiyoshi
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzu
authors.forename: Anucha
authors.initials: A
authors.lastname: Puapairoj
authors.forename: Chairisi
authors.initials: C
authors.lastname: Wongkham
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D031607:Stephania / Q000737:chemistry; D013785:Thailand / Q000453:epidemiology; D052117:Benzodioxoles
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D016328:NF-kappa B; C006947:cepharanthine; D052117:Benzodioxoles
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