title: EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma.
abstract: A synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment.
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.|Department of Pharmacology, The State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
authors: Da-Long
authors: DL
authors: Yin
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.
authors: Ying-Jian
authors: YJ
authors: Liang
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.
authors: Tong-Sen
authors: TS
authors: Zheng
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.|Department of Pharmacology, The State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
authors: Rui-Peng
authors: RP
authors: Song
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.
authors: Jia-Bei
authors: JB
authors: Wang
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.
authors: Bo-Shi
authors: BS
authors: Sun
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.
authors: Shang-Ha
authors: SH
authors: Pan
authors: National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, P.R. China.
authors: Lian-Dong
authors: LD
authors: Qu
authors: Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.
authors: Jia-Ren
authors: JR
authors: Liu
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.
authors: Hong-Chi
authors: HC
authors: Jiang
authors: Department of General Surgery, the First Affiliated Hospital of Harbin Medical University; Key Laboratory of Hepatosplenic Surgery, Ministry of Education. No23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, P.R.China.|Department of Pharmacology, The State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
authors: Lian-Xin
authors: LX
authors: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001597:Benzylidene Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010881:Piperidones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: C524042:3,5-bis(2-fluorobenzylidene)piperidin-4-one; D001597:Benzylidene Compounds; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010881:Piperidones