title: Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation.
abstract: BACKGROUND
  Although radiotherapy is one of the mainstream approaches for the treatment of head and neck squamous cell carcinoma (HNSCC), this cancer is always associated with resistance to radiation. In this study, the mechanism of action of isoalantolactone as well as its radiosensitizing effect was investigated in UMSCC-10A cells.
  
  
  METHODS
  The radiosensitization of UMSCC-10A cells treated with isoalantolactone was analyzed by colony formation assay. The radiosensitization effects of isoalantolactone on cell proliferation, cell cycle and apoptosis regulation were examined by BrdU incorporation assay, DNA content assay and flow cytometry, respectively. Western blotting was performed to determine the effects of isoalantolactone combined with radiation on the protein expression of Mek, extracellular signal-regulated kinase (Erk1/2) as well as phosphorylated Mek and Erk1/2. Erk1/2 knockdown by siRNA was used to confirm that isoalantolactone specifically inhibited the activation of Erk1/2 signaling pathway in UMSCC-10A cells.
  
  
  RESULTS
  Isoalantolactone enhanced the radiosensitivity of UMSCC-10A cells; the sensitivity enhanced ratios (SERs) were 1.44 and 1.63, respectively, for 2.5 and 5 μM. Moreover, isoalantolactone enhanced radiation-induced cell proliferation and apoptosis and cell cycle arrested at G2/M phase. Furthermore, no marked changes were observed in the expression of total Erk1/2 and Mek protein after radiation treatment. However, isoalantolactone was significantly reduced radiation-induced the phosphorylation of Erk1/2, whereas it altered the phosphorylation of Mek to a lesser extent. In addition, the radiosensitivity of UMSCC-10A cells with Erk1/2 knockdown was increased. Isoalantolactone cannot further prevent the proliferation of UMSCC-10A cells with Erk1/2 knockdown which other mechanism regulated cell proliferation.
  
  
  CONCLUSIONS
  Our results suggested that isoalantolactone enhanced radiation-induced apoptosis, cell cycle arrested and reduced the cell proliferation of UMSCC-10A cells via specifically inhibited the phosphorylation of Erk1/2. Thus a low concentration of isoalantolactone may be used to overcome the resistance of UMSCC-10A cells to radiation and may be a promising radiosensitizer in cancer therapy.
authors.affiliation: Department of Cell Biology, Liaoning Medical University, Jinzhou, Liaoning, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Cell Biology, Liaoning Medical University, Jinzhou, Liaoning, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Department of clinical laboratory, Daqing oilfield general hospital, Daqing, Heilongjiang, China.
authors.forename: Hongguo
authors.initials: H
authors.lastname: Gao
authors.affiliation: Information Center, Logistics college, Naval University of Engineering, Tanggu, Tianjin, China.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of clinical laboratory, Daqing oilfield general hospital, Daqing, Heilongjiang, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Liaoning Medical University, Jinzhou, Liaoning, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Liaoning Medical University, Jinzhou, Liaoning, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D011838:Radiation-Sensitizing Agents; D012717:Sesquiterpenes; C032787:isoalantolactone; D048049:Extracellular Signal-Regulated MAP Kinases