Virtual Library

Start Your Search

Y. Tzur



Author of

  • +

    P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
    • +

      P2.04-047 - Mitochondrial Activation- A Potential Therapy in Lung Cancer (ID 2359)

      09:30 - 09:30  |  Author(s): Y. Tzur

      • Abstract
      • Slides

      Background:
      Lung cancer is the leading cause of cancer related deaths in the United States with an overall 5- year survival rate of all stages of~ 17%. Radiation therapy plays a key role in lung cancer treatment. However, many lung cancer patients show resistance to radiation. There is a growing body of evidence indicating that mitochondria may be the primary targets for cancer therapeutics: The unique metabolism of most solid tumors, including lung cancer, stems from remodeling mitochondrial functions to produce a glycolytic phenotype and a strong resistance to apoptosis (Warburg effect). Cancer specific remodeling can be reversed by a small molecule named dichloroacetate (DCA) which promote mitochondrial activation by increasing the influx of pyruvate. Sodium oxamate- another molecule that interferes with cells metabolism, inhibits the formation of the lactate-the end product of glycolysis. Here, we tested whether mitochondrial induction (using DCA and sodium oxamate) may increase the sensitivity of non-small cell lung cancer (NSCLC) cells to radiation through this mechanism. Moreover we tested whether sodium oxamate, increases the effect of DCA on radiation.

      Methods:
      Two representative NSCLC cell lines (A549 and H1299) were tested for their sensitivity to radiation with and without pre-exposure to DCA and sodium oxamate. 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. Sodium Oxamate radisosensitized H1299 cells as well. Double treatment with DCA and Sodium Oxamate enhances the radiosensitivity of H1299 cells.

      Conclusion:
      Mitochondrial activation may serve as a radio-sensitizer in the treatment of non-small cell lung cancer. Inhibition of the end stage of glycolysis increases the effect of mitochondrial activation on radiation.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.