title: A new synthetic ursolic acid derivative IUA with anti-tumor efficacy against osteosarcoma cells via inhibition of JNK signaling pathway.
abstract: BACKGROUND
  Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and is characterized by frequent metastasis and resistance to chemotherapy. Because osteosarcoma cells are not highly susceptible to current chemotherapy drugs, new alternative strategies for the treatment of osteosarcoma are needed. This study was undertaken to investigate the inhibitory effects of a new synthetic ursolic acid derivative IUA on osteosarcoma cells and to explore its molecular mechanism. We also intended to identify new therapeutic candidates.
  
  
  METHODS
  We used MTT assay to assess the effect of IUA on the proliferation of osteosarcoma cells. Western-blot analysis was performed to examine downstream molecular events. The Annexin V method was used to evaluate the effect of IUA on apoptosis of osteosarcoma cells. The cell cycle of IUA-treated cells was examined by flow cytometry, and the in vivo effects of this new ursolic acid derivative were evaluated in a mouse osteosarcoma model.
  
  
  RESULTS
  The results showed that the new synthetic ursolic acid derivative IUA significantly decreased viability of osteosarcoma cells in vitro and in vivo. It could also induce apoptosis and G1 phase arrest of osteosarcoma cells. The JNK signaling pathway was significantly inhibited, and cleaved caspase-3 protein was increased.
  
  
  CONCLUSIONS
  We concluded that the new synthetic ursolic acid derivative IUA induces proliferation inhibition and apoptosis of osteosarcoma cells in vitro and in vivo via the down-regulation of the JNK signaling pathway, making it a promising agent for the prevention and treatment of human osteosarcoma.
authors.affiliation: Department of Orthopaedics, Shanghai First People's Hospital, Nanjing Medical University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Haijian
authors.initials: H
authors.lastname: Fu
authors.forename: Zhuoying
authors.initials: Z
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Hua
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D048670:MAP Kinase Kinase 4; D014315:Triterpenes; D000097245:Ursolic Acid