Figure 7. Gossypol combined with phenformin reversed NSCLC through induction of cell death via ATP depletion.
(A) Effect of gossypol (10 μM), phenformin (100 μM), or combined treatment for 48 h on cell death as determined by flow cytometric analysis and ATP production by ATP assay. (B) IVIS imaging of A549-luciferase xenograft tumors was taken. When the tumor mass volume reached to 100 mm3, the mice were treated orally 7 days/week. (n = 7 per each group). The dissemination of cells into lungs was monitored by IVIS (Xenogen). The data were expressed as photon flux (photons/s/cm2/steradian), and photon flux for each measurement is represented by a colour scale. (C) Tumor volumes were determined as described in Materials and Methods. (D) Proposed model for the role of ALDH in NSCLC metabolism. ALDH1L1 plays a key role in ATP synthesis through NADH production. NADH produced in the cytosol needs to be transported into the mitochondria by the malate-aspartate shuttle for ATP production. Data are representative of the mean and standard deviation three independent experiments. **p < 0.01, ***p < 0.001 compared to vehicle control.