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F. Cerqueira
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-067 - Mitochondrial Respiration Capacity and Sensitivity to Glycolysis Blockade in Lung Cancer (ID 2360)
09:30 - 17:00 | Author(s): F. Cerqueira
- Abstract
Background:
One of the metabolic perturbations in cancer cells is the Warburg effect; glycolysis is preferred over oxidative phosphorylation (OXPHOS), even in the presence of oxygen. The precise mitochondrial alterations that underlie the increased dependence of cancer cells on aerobic glycolysis for energy generation may serve as an escape mechanism from apoptosis. Here, we aimed to profile the mitochondrial activity in different lung cancer cell lines in reference to their glycolytic activity and to their sensitivity to metabolic modifications.
Methods:
The metabolic profile of A549 and H358 cell lines were tested before and after glycolysis blockade (glucose starvation, 2DG) and mitochondrial induction (FCCP). Glycolysis inhibition and mitochondrial activity were assessed by western-blot quantification of key enzymes involved in the glycolysis pathway (e.g. Hexokinase I/II, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase 2) and of mitochondrial coded proteins (e.g. ND1, ATP6 synthase). The oxygen consumption rates (OCR) and extra cellular acidification rate (ECAR) were measured by XF[e]24 extracellular flux analyzer. Further, mitochondrial index was compared to the cells' sensitivity to glycolysis inhibition.
Results:
A549 cells were highly affected by glucose inhibition/starvation accompanied by ineffective mitochondrial compensation. On the other hand, H358 cells recovered completely from glucose starvation through mitochondrial hyper-activation (Fig 1); At the basal level (when no material was applied), A549 cells that were starved had a decrease of 68% in the ECAR, as compared to non-treated cells. Their recovery was limited after glucose injection (23 vs.41 mpH/min). In comparison, H358 cells had a 43% decrease in their glycolysis rate with a full recovery after glucose injection (44-46 mpH/min; pre & post respectively). Mitochondrial respiration was very low for A549 cells under starvation, while significantly increased in H358 cells (223 vs.143 pmol/min, *Pv<0.0001). Respectively, the expression level of mitochondrial coded proteins was higher in the cells that demonstrated higher mitochondrial capacity (Fig 2). Figure 1
Conclusion:
Cells with high mitochondrial capacity may tolerate glucose starvation/ blockade, while a limited mitochondrial reserve exposes the cells to higher sensitivity to glycolysis stress. This might suggest a potential therapeutic avenue with a companion predictive test.
