title: Synergistic effect of ethaselen and selenite treatment against A549 human non-small cell lung cancer cells.
abstract: BACKGROUND
  In this study, we aimed to evaluate the growth inhibitory effect of the combination of ethaselen (BBSKE) and low fixed dose of selenite against A549 human non-small cell lung cancer cells in vitro.
  
  
  METHODS
  Growth inhibitory effects against A549 cells were determined by SRB assay. Combination index (CI) values were calculated based on Chou-Talalay median-effect analyses. Dose reduction index (DRI) values were applied to calculate dose reduction of selenite. Contents of free thiols and GSH were determined by DTNB assay and intracellular ROS levels by DCFH-DA fluorescence labeling.
  
  
  RESULTS
  Compared with BBSKE or selenite single treatment, the combined application of ethaselen and a low fixed dose of selenite shortened the onset time of sodium selenite, reduced IC50 values, and increased the maximum inhibition rates, suggesting a possible molecular mechanism of the synergism. Obvious synergistic effects were observed after different times of combination treatment, especially after 24 h. Compared with selenite single treatment, dosage of selenite could be remarkably reduced in combination therapy to gain the same inhibitory effect on cell proliferation. Compared with BBSKE single treatment, the content of free thiols and GSH were significantly reduced and ROS levels greatly elevated in the combination group. For the combination treatment, cell viability increased as greater concentrations of GSH were added.
  
  
  CONCLUSIONS
  All these results indicate that the combination treatment of BBSKE and selenite showed synergism to inhibit A549 cell proliferation in vitro, and also reduced the selenite dosage to mitigate its toxicity which is very meaningful for combination chemotherapy of lung cancer. The synergism was probably caused by the accelerated exhaustion of intracellular reductive substances, such as free thiols and GSH, which ultimately leads to enhanced oxidative stress and apoptosis.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China E-mail : zenghh@bjmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Ma
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Zeng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms; D016566:Organoselenium Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020887:Selenious Acid / Q000494:pharmacology*
chemical_list: C478160:(1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone))ethane; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D020887:Selenious Acid