title: Mitochondrial induction as a potential radio-sensitizer in lung cancer cells - a short report.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer death. Radiation therapy plays a key role in its treatment. Ionizing radiation induces cell death through chromosomal aberrations, which trigger mitotic catastrophe and apoptosis. However, many lung cancer patients show resistance to radiation. Dichloroacetate (DCA) is a small molecule that can promote mitochondrial activation by increasing the influx of pyruvate. Here, we tested whether DCA may increase the sensitivity of non-small cell lung cancer (NSCLC) cells to radiation through this mechanism.
  
  
  METHODS
  Two representative NSCLC cell lines (A549 and H1299) were tested for their sensitivity to radiation with and without pre-exposure to DCA. The treatment efficacy was evaluated using a clonogenic survival assay. An extracellular flux analyzer was used to assess the effect of DCA on cellular oxygen consumption as a surrogate marker for mitochondrial activity.
  
  
  RESULTS
  We found that DCA increases the oxygen consumption rate in both A549 and H1299 cells by 60% (p = 0.0037) and 20% (p = 0.0039), respectively. Pre-exposure to DCA one hour before radiation increased the cytotoxic death rate 4-fold in A549 cells (55 to 13%, p = 0.004) and 2-fold in H1299 cells (35 to 17%, p = 0.28) respectively, compared to radiation alone.
  
  
  CONCLUSIONS
  Mitochondrial induction by DCA may serve as a radio-sensitizer in non-small cell lung cancer.
authors.affiliation: Thoracic Cancer Research and Detection Center, Sheba Medical Center Tel Hashomer, Ramat-Gan, 52621, POB 244, Israel.
authors.forename: Ronen
authors.initials: R
authors.lastname: Shavit
authors.forename: Maya
authors.initials: M
authors.lastname: Ilouze
authors.forename: Tali
authors.initials: T
authors.lastname: Feinberg
authors.forename: Yaacov Richard
authors.initials: YR
authors.lastname: Lawrence
authors.forename: Yossi
authors.initials: Y
authors.lastname: Tzur
authors.forename: Nir
authors.initials: N
authors.lastname: Peled
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D011838:Radiation-Sensitizing Agents; D003999:Dichloroacetic Acid