title: Anti-cancer effect of N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxamide, a novel synthetic compound.
abstract: Naphthofuran compounds have been known to regulate HNF 4α which is associated with proliferation, progression and metastasis of HCC. In this study, we investigated whether N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxamide (NHDC), a novel synthetic naphthofuran compound inhibits liver tumor growth through activation of HNF 4α. Treatment with different concentrations (1-10.8 µM) of NHDC for various periods (0-72 h) inhibited liver cancer cells (HepG2, Hep3B) growth as well as colony formation followed by induction of apoptosis in a concentration dependent manner. NHDC also induced expression of the apoptosis regulating genes as well as inhibiting the action of STAT3. These inhibitory effects were associated with enhancement of expression and DNA binding activity of HNF 4α. In vivo study confirmed that liver tumor growth was prevented with NHDC (5 mg/kg), and its effect was also related with inhibition of STAT3 pathway through enhancement of expression and DNA binding activity of HNF 4α. Moreover, siRNA of HNF 4α abolished NHDC-induced cell growth inhibition as well as DNA binding activity and phosphorylation of STAT3. Pull down assay docking prediction analysis proved that NHDC directly binds to hydrophobic fatty acid ligand binding site of HNF 4α. A novel naphthofuran compound, NHDC inhibited liver tumor growth by inactivating of STAT3 through direct biding to HNF 4α.
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Sun Mi
authors: SM
authors: Kwon
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Yu Yeon
authors: YY
authors: Jung
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Chul Ju
authors: CJ
authors: Hwang
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Mi Hee
authors: MH
authors: Park
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Na Young
authors: NY
authors: Yoon
authors: College of Veterinary Medicine, Chungbuk National University, Chungbuk, Korea.
authors: Tae Myung
authors: TM
authors: Kim
authors: College of Veterinary Medicine, Chungbuk National University, Chungbuk, Korea.
authors: Ji Myung
authors: JM
authors: Yu
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Dae Hwan
authors: DH
authors: Kim
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Doo Won
authors: DW
authors: Seo
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Hyu Seok
authors: HS
authors: Youn
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Hyun Ok
authors: HO
authors: Seo
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: In Sung
authors: IS
authors: Chung
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Sang Bae
authors: SB
authors: Han
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Bang Yeon
authors: BY
authors: Hwang
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Hwan-Soo
authors: HS
authors: Yoo
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Jae-Kyung
authors: JK
authors: Jung
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Heesoon
authors: H
authors: Lee
authors: College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk, Korea.
authors: Jin Tae
authors: JT
authors: Hong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009281:Naphthalenes / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D009284:Naphthols / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; C000610846:NHDC compound; D009281:Naphthalenes; D009284:Naphthols; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: HNF 4α; NHDC; STAT3; naphthofuran; tumor growth