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
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P2.04-047 - Mitochondrial Activation- A Potential Therapy in Lung Cancer (ID 2359)
09:30 - 09:30 | Author(s): Y. Tzur
- Abstract
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.
