EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma
| Autor: | Shang Ha Pan, Tong Sen Zheng, Lianxin Liu, Jia Bei Wang, Hongchi Jiang, Ying Jian Liang, Rui Peng Song, Lian Dong Qu, Da Long Yin, Jiaren Liu, Bo Shi Sun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Apoptosis Biology Inhibitor of apoptosis medicine.disease_cause Benzylidene Compounds Article Metastasis Cholangiocarcinoma 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine Humans Neoplasm Metastasis Piperidones Multidisciplinary Cell growth NF-kappa B medicine.disease XIAP Cell biology Neoplasm Proteins G2 Phase Cell Cycle Checkpoints 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell M Phase Cell Cycle Checkpoints Signal transduction Carcinogenesis Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep32167 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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