Mitochondrial induction as a potential radio-sensitizer in lung cancer cells - a short report

Abstract

Mitochondrial induction by DCA may serve as a radio-sensitizer in non-small cell lung cancer.

Dichloroacetate alters Warburg metabolism, inhibits cell growth, and increases the X-ray sensitivity of human A549 and H1299 NSC lung cancer cells

“…Based on these results, we performed all remaining studies with A549 and H1299 lung adenocarcinoma cells with 50 mM DCA. A very recent study by Shavit et al in 2015 has confirmed similar IC 50 values in vitro for both A549 and H1299 cells [31].…”

“…Some studies indicate that targeting cancer cell Warburg metabolism with metabolic agents has therapeutic potential especially in combination with radiation or chemotherapy [14][15][16][17][18][19]31]. DCA is a synthetic small molecule that has high bioavailability and is currently being used to treat hereditary metabolic or cardiovascular diseases [26,27].…”

“…Data indicate that DCA reduces lactate production in cancer cells by inhibiting the mitochondrial enzyme pyruvate dehydrogenase kinase that results in an (unphosphorylated) active pyruvate dehydrogenase complex (PDC) that increases pyruvate oxidation in the mitochondria, promotes glucose oxidation, and decreases lactate production in the cell cytoplasm, resulting in an overall increase in oxidative phosphorylation [19,26,30]. However, the true potential for metabolic drugs such as DCA may be as an adjunct to chemotherapy and radiation in multimodality cancer treatment, although to date results have been mixed [14][15][16][17][18][19][20][21]31].…”

Sensitization of Glioblastoma Cells to Irradiation by Modulating the Glucose Metabolism

“…Dichloroacetate, a PDK inhibitor that has the potential for such metabolic targeting, has been shown to reverse the Warburg effect by shifting glucose metabolism from glycolysis to mitochondrial oxidation and to inhibit tumor cell growth (9,10). By combining with radiotherapy, dichloroacetate has been demonstrated to enhance the radiosensitivity of several tumor types in vitro (11)(12)(13). Interestingly, a previous study using 2 human cancer cell lines (colon adenocarcinoma and glioblastoma) demonstrated that dichloroacetate sensitized the efficacy of radiotherapy in vitro but attenuated radiotherapy-induced tumor growth delay in vivo (colon adenocarcinoma model; ref.…”

Anti-tumor effect of emodin on gynecological cancer cells

“…Apoptosis is mediated by either an extrinsic pathway, triggered by extracellular stimuli, or by an intrinsic pathway, activated by intracellular modulators [20][21][22][23]. Mitochondria play a critical role in the intrinsic pathway by releasing a series of molecules, including cytochrome c. Within the cytosol, the binding of cytochrome c to adaptor protein Apaf-1 and pro-caspasse-9 molecules leads to the formation of the apoptosome that is responsible for activation of a caspase-dependent apoptotic pathway [24].…”