title: Xanthohumol inhibits STAT3 activation pathway leading to growth suppression and apoptosis induction in human cholangiocarcinoma cells.
abstract: STAT3 plays a significant role in the development of cholangiocarcinoma (CCA) associated with the liver fluke (Opisthorchis viverrini; Ov). Xanthohumol (XN), a prenylated flavonoid extracted from hops, has known anticancer activity and could potentially target STAT3. The present study determined the effect of XN on STAT3, as well as ascertained its usefulness against CCA. The CCA cell proliferation at 20 µM and 50 µM of XN was shown to inhibited, while 20 µM partially inhibited IL-6-induced STAT3 activation. At 50 µM, the inhibition was complete. The reduction in STAT3 activity at 20 and 50 µM was associated with a significant reduction of CCA cell growth and apoptosis. We also found that the administration of 50 µM XN orally in drinking water to nude mice inoculated with CCA led to a reduction in tumor growth in comparison with controls. In addition, apoptosis of cancer cells increased although there was no visible toxicity. The present study shows that XN can inhibit STAT3 activation both in vivo and in vitro due to suppression of the Akt-NFκB signaling pathway. XN should be considered as a possible therapeutic agent against CCA.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Hasaya
authors.initials: H
authors.lastname: Dokduang
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Sakkarn
authors.initials: S
authors.lastname: Sangkhamanon
authors.affiliation: Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Mika Sakurai
authors.initials: MS
authors.lastname: Yageta
authors.affiliation: Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D011427:Propiophenones / Q000008:administration & dosage* / Q000494:pharmacology; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C576601:ARHGEF3 protein, human; D000970:Antineoplastic Agents; D005419:Flavonoids; D011427:Propiophenones; D064067:Rho Guanine Nucleotide Exchange Factors; C104536:xanthohumol