title: Anti-tumor effects of Atractylenolide I on bladder cancer cells.
abstract: BACKGROUND
  Atractylenolide I (ATR-1), an active component of Rhizoma Atractylodis Macrocephalae, possesses cytotoxicity against various carcinomas. However, little is known about the effects of ATR-1on bladder cancer. In the present study, the anti-tumor activity of ATR-1 was examined on bladder cancer cells both in vivo and in vitro.
  
  
  METHODS
  MTT assay was used to assess the cytotoxic effect of ATR-1. Cell cycle distribution and apoptosis levels were evaluated using flow cytometry. Western blotting assay was applied to measure the levels of proteins associated with the apoptotic pathway, cell cycle progression and PI3K/Akt/mTOR signaling pathway. Tumor models in nude mice were induced by injection of T-24 and 253J human bladder cancer cells.
  
  
  RESULTS
  ATR-1 inhibited bladder cancer cell proliferation, arrested cell cycle in G2/M phase through up-regulation of p21 and down-regulation of cyclin B1, CDK1 and Cdc25c. Meanwhile, ATR-1 also triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Mechanism investigation indicated that ATR-1 exerts its anti-tumor effect also relies on the inhibition of PI3K/Akt/mTOR signaling pathway. Finally, mice studies showed that ATR-1 blocked the T-24 or 253J-induced xenograft tumor growth without noticeable toxicity.
  
  
  CONCLUSIONS
  ATR-1 may be served as a potential therapeutic agent for the treatment of bladder cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Fenghua St., 315211, Ningbo, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China.
authors.forename: Bi-Xia
authors.initials: BX
authors.lastname: Yu
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Chen
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China.
authors.forename: Xiu-Yi
authors.initials: XY
authors.lastname: Lv
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China.|Department of Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China.
authors.forename: Ze-Jun
authors.initials: ZJ
authors.lastname: Yan
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China. chengyue131@yahoo.com.|Department of Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China. chengyue131@yahoo.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China. qi.ma505@yahoo.com.|Department of Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Liuting St., 315010, Ningbo, China. qi.ma505@yahoo.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D007783:Lactones; D012717:Sesquiterpenes; C424804:atractylenolide I