Reduced Warburg Effect in Cancer Cells Undergoing Autophagy: Steady- State 1H-MRS and Real-Time Hyperpolarized 13C-MRS Studies
Figure 5
Assessment of apparent 13C-pyruvate to lactate exchange rate.
(a) Hyperpolarized 13C-spectrum from an HCT116 Bax-ko cell assay showing the sum over the entire dynamic time series from a control cell experiment, following 6 hr starvation, 24 hr starvation with HBSS media and after 24 hr starvation followed by 48 hr cell recovery. The spectrum displays peaks from pyruvate (Pyr), lactate (Lac) and pyruvate hydrate (Pyr H). (b) Plot of the lactate peak integral as a function of time normalized to the pyruvate peak integral at time t = 0 s and normalized per million cells acquired for HCT116 Bax-ko control cells, 24 hr starvation with HBSS media and 24 hr starvation followed by 48 hr recovery. (c) The mean ratios (treated/24 hr vehicle-control) of the apparent forward reaction rate of pyruvate to lactate exchange kPL (derived from fitting of the experimental data and normalized to cell number) (± s.e.m.) for 24 hr DMSO-treated recovery, 100 μM PI-103 treated and 48 hr recovery following 100 μM PI-103 treatment in HT29 cells; for 10 μM PI-103 treated, 20 μM PI-103 treated and 48 hr recovery following 20 μM PI-103 treatment in HCT116 Bax-ko cells; and for 6 hr HBSS starvation, 24 hr HBSS starvation and 24 hr starvation followed by 48 hr recovery in HCT116 Bax-ko cells. Minimum n = 3 in each group. Statistically significant changes are indicated (*p≤0.05).