title: Chloroquine exerts anti-metastatic activities under hypoxic conditions in cholangiocarcinoma cells.
abstract: Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial- mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride (CoCl2)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to 100 μM CoCl2. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-1α/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand E-mail : nisana@kku.ac.th.
authors.forename: Suyanee
authors.initials: S
authors.lastname: Thongchot
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.forename: Hasaya
authors.initials: H
authors.lastname: Dokduang
authors.forename: Raynoo
authors.initials: R
authors.lastname: Thanan
authors.forename: Anchalee
authors.initials: A
authors.lastname: Techasen
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology*; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D015820:Cadherins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D002738:Chloroquine