title: β-Elemene induces apoptosis in human renal-cell carcinoma 786-0 cells through inhibition of MAPK/ERK and PI3K/Akt/ mTOR signalling pathways.
abstract: BACKGROUND
  Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. β-Elemene, a promising anticancer drug extracted from a traditional Chinese medicine, has been shown to be effective against various tumors. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated.
  
  
  METHODS
  Human RCC 786-0 cells were treated with different concentrations of β-elemene, and cell viability and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by western blotting. Autophagy was evaluated by transmission electron microscopy.
  
  
  RESULTS
  β-Elemene inhibited the viability of 786-0 cells in a dose- and time-dependent manner. The anti-tumor effect was associated with induction of apoptosis. Further study showed that β-elemene inhibited the MAPK/ERK as well as PI3K/Akt/mTOR signalling pathways. Moreover, robust autophagy was observed in cells treated with β-elemene. Combined treatment of β-elemene with autophagy inhibitors 3-methyladenine or chlorochine significantly enhanced the anti-tumor effects.
  
  
  CONCLUSIONS
  Our data provide first evidence that β-elemene can inhibit the proliferation of RCC 786- 0 cells by inducing apoptosis as well as protective autophagy. The anti-tumor effect was associated with the inhibition of MAPK/ERK and PI3K/Akt/mTOR signalling pathway. Inhibition of autophagy might be a useful way to enhance the anti-tumor effect of β -elemene on 786-0 cells.
authors.affiliation: Department of Urology, the Shengjing Hospital, China.
authors.forename: Yun-Hong
authors.initials: YH
authors.lastname: Zhan
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Qu
authors.forename: Ke-Zuo
authors.initials: KZ
authors.lastname: Hou
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Wang
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000225:Adenine; D002738:Chloroquine; D048049:Extracellular Signal-Regulated MAP Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012717:Sesquiterpenes; D058570:TOR Serine-Threonine Kinases; C445979:beta-elemene; C025946:3-methyladenine; C546842:MTOR protein, human