title: Cratoxylum formosum Extracts Inhibit Growth and Metastasis of Cholangiocarcinoma Cells by Modulating the NF-κB and STAT3 Pathways.
abstract: Cratoxylum formosum Dyer has been used in Southeast Asian countries both for food and folk medicine. In this study, the leaf extracts of C. formosum were evaluated for anticancer effects on human cholangiocarcinoma (CCA) KKU-M156 cells. The results showed that the plant extracts possessed potent cytotoxicity against CCA cells. The cytotoxic activity was associated with an induction of cell apoptosis. Moreover, the colony forming ability of CCA cells was also inhibited by C. formosum extracts. Consistent with growth inhibitory effects, the plant extracts induced cell cycle arrest at the G2/M phase and downregulated cyclin A and Cdc25A protein expression. The extracts potently suppressed the migration and invasion properties of CCA cells. The effects were associated with the suppression of NF-κB and STAT3 nuclear translocation and transcriptional activity, and downregulation of genes involving in cancer progression and metastasis. Furthermore, the possible bioactive compounds in the extracts were analyzed by HPLC. Taken together, the potent anticancer activity of C. formosum against CCA indicates the plant promising use for CCA prevention and therapy.
authors.affiliation: a Department of Pharmacology , Faculty of Medicine, and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University , Khon Kaen , Thailand.
authors.forename: Laddawan
authors.initials: L
authors.lastname: Senggunprai
authors.affiliation: b Department of Pharmacology , Faculty of Medicine, Khon Kaen University , Khon Kaen , Thailand.
authors.forename: Wachiraporn
authors.initials: W
authors.lastname: Thammaniwit
authors.affiliation: c Department of Pharmacology , Faculty of Medicine, and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University , Khon Kaen , Thailand.
authors.forename: Veerapol
authors.initials: V
authors.lastname: Kukongviriyapan
authors.affiliation: c Department of Pharmacology , Faculty of Medicine, and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University , Khon Kaen , Thailand.
authors.forename: Auemduan
authors.initials: A
authors.lastname: Prawan
authors.affiliation: d Department of Chemistry , Faculty of Science, Mahasarakham University , Maha Sarakham , Thailand.
authors.forename: Niwat
authors.initials: N
authors.lastname: Kaewseejan
authors.affiliation: e Department of Food Technology and Nutrition , Faculty of Technology, Mahasarakham University , Maha Sarakham , Thailand.
authors.forename: Sirithon
authors.initials: S
authors.lastname: Siriamornpun
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D028084:Clusiaceae / Q000737:chemistry*; D019925:Cyclin A / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005419:Flavonoids / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D062385:Hydroxybenzoates / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019925:Cyclin A; D005419:Flavonoids; D062385:Hydroxybenzoates; D016328:NF-kappa B; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C017616:phenolic acid