title: Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy.
abstract: OBJECTIVE
  To elucidate the underlying events in Chlorin e6 (Ce6)-mediated sonodynamic therapy (SDT) (Ce6-SDT)-induced apoptosis of human leukemia cell line U937.
  
  
  METHODS
  The viability of cells was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide tetrazolium (MTT) test. Apoptosis was analyzed using a ﬂow cytometer as well as ﬂuorescence microscopy with 4'-6-Diamidino-2-Phenylindole (DAPI) staining. Western blotting was used to analyze the expression of caspase-3, poly ADP- ribose polymerase (PARP) and mitogen-activated protein kinase (MAPK).
  
  
  RESULTS
  Several distinct sonochemical effects were found after SDT treatment. The participation of MAPK signals in SDT which caused U937 cell damage was specifically examined and the inhibition of p38 MAPK and Jun-N-terminal kinase (JNK) both apparently exerted a negative effect on SDT-induced cell death, while extracellular signal-regulating kinase (ERK1/2) inhibition enhanced SDT-induced cell death. The intracellular reactive oxygen species (ROS) was significantly enhanced by SDT, and pre-treatment with ROS scavenger N-acetylcysteine (NAC) partially alleviated SDT-induced cell viability loss, DNA fragmentation, mitochondria membrane potential (MMP) dissipation, caspase-3 activation, but interestingly MAPK activation was not affected much by NAC.
  
  
  CONCLUSIONS
  In the present paper, cell apoptosis of U937 cells was markedly enhanced after Ce6-SDT. Meanwhile, p38 MAPK, JNK and ERK were all differently activated in this process. One possible explanation for the induced cell apoptosis could be the increased ROS generation in Ce6-SDT.
authors.affiliation: Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University , Xi'an , P. R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Su
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.forename: Silu
authors.initials: S
authors.lastname: Li
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D001692:Biological Transport; D002735:Chlorophyllides; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010778:Photochemotherapy; D011166:Porphyrins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020298:U937 Cells; D014465:Ultrasonics
chemical_list: D002735:Chlorophyllides; D011166:Porphyrins; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; C062985:phytochlorin; D020928:Mitogen-Activated Protein Kinases