title: BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus.
abstract: BHX (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide), a Wnt signaling pathway inhibitor, effectively inhibits tumor cell growth, but the underlying mechanism is unclear. Thus, we aim to investigate the effects and associated mechanism of BHX action on A549 and MCF-7 cell lines. In our study, MTT(3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) and xenograft model assay indicated that cell growth was inhibited by BHX at a range of concentrations in vitro and in vivo. The expression of β-catenin and Wnt signaling pathway downstream target genes were decreased evidently under BHX treatment. Flow cytometry also revealed that BHX treatment significantly induced G1 arrest. Further analysis showed that BHX lowered the transcriptional level of β-catenin. In conclusion, BHX inhibited the nuclear synthesis of β-catenin, thereby suppressing the Wnt signaling pathway and further inhibiting tumor growth and proliferation.
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P. R. China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P. R. China.
authors.forename: Meisa
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P. R. China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P. R. China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P. R. China.
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Clinical Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P. R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yan
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D011720:Pyrazoles / Q000494:pharmacology*; D015398:Signal Transduction; D047368:Tumor Burden / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; C000589318:N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide; D011720:Pyrazoles; D051153:Wnt Proteins; D051176:beta Catenin