Article Figures & Data
Figures
- FIGURE 1.
Resveratrol (RSV) reduces ROS, which is sufficient to suppress glucose uptake. (A) Dose- (left) and time-dependent (middle) effects of resveratrol on LLC cell ROS concentration as measured by fluorescent CM-DCHF-DA assays. ROS concentration and 18F-FDG uptake in resveratrol-treated cells show high correlation (right). (B) ROS concentration (left) and 18F-FDG uptake (middle) in LLC cells treated for 24 h with 50 μM resveratrol or vehicle in presence or absence of ROS scavenger N-acetylcysteine (NAC; 10 mM). Effects of NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin (ACN) on 18F-FDG uptake (right). All results are mean ± SD of triplicate samples expressed as percentage relative to controls obtained from single representative experiment of 2 separate experiments. **P < 0.01, ***P < 0.001, †P < 0.0005, ‡P < 0.0001, compared with controls.
- FIGURE 2.
Reduction of ROS and HIF-1α is required for metabolic effect of resveratrol (RSV). (A) ROS inducers increase basal 18F-FDG uptake and restore uptake in resveratrol-treated LLC cells. Hydrogen peroxide (H2O2; 200 μM), tert-butylhydroperoxide (tBHP; 20 μM), or 3-(4-morpholinyl)sydnonimine (SIN-1; 100 μM) was added to cells 1 h before initiation of treatment with 50 μM resveratrol. (B) HIF-1α accumulation (top) and 18F-FDG uptake (bottom) after 24-h treatment with 50 μM resveratrol or vehicle in presence or absence of cycloheximide (10 μM for 24 h; left) or proteasome inhibitor MG132 (10 μM for 4 h; right). Bars are mean ± SD of triplicate samples expressed as percentage relative to controls. *P < 0.05, **P < 0.01, †P < 0.0005, ‡P < 0.0001, compared with controls. n.s. = not significant.
- FIGURE 3.
Roles of HIF-1α, PI3K/Akt, and mTOR signaling on resveratrol (RSV) effect. (A) Effects of HIF-1α and PI3K silencing with specific siRNA on 18F-FDG uptake. (B) Immunoblots showing effects of graded resveratrol doses on phosphorylated Akt (pAkt), Akt, HIF-1α, and mTOR expression (left) and time-dependent effects of 50 μM resveratrol on pAkt, Akt, and HIF-1α expression (right). β-actin was used as loading control. (C) Effects of PI3K inhibition with wortmannin or LY294002 and mTOR inhibition with rapamycin on 18F-FDG uptake of cells treated with 50 μM resveratrol or vehicle. All bars are mean ± SD of triplicate samples expressed as percentage relative to controls obtained from single experiment representative of 2 separate experiments. *P < 0.05, **P < 0.01, †P < 0.0005, ‡P < 0.0001, compared with controls.
- FIGURE 4.
Effects of resveratrol (RSV) on glucose metabolism of LLC cells. (A) Western blots showing time-dependent Glut-1 expression after resveratrol treatment. (B) Effects of resveratrol on lactate production (left) and oxygen consumption rate (right). (C) Effects of resveratrol on 18F-FDG uptake (left) and hexokinase activity (right) with 1-h treatment with 1 mM of 3-bromopyruvate (3BrPA) as positive control. Bars are mean ± SD of triplicate samples obtained from single experiment representative of 2 or 3 separate experiments (B) or mean ± SE of 6 samples obtained from 2 independent experiments (C). †P < 0.0005, ‡P < 0.0001, compared with controls. n.s. = not significant.
- FIGURE 5.
Sequential 18F-FDG PET in tumor-bearing BALB/C mice after treatment with resveratrol (RSV) and vehicle. (A and B) Coronal small-animal PET tomographs showing subcutaneously implanted LLC tumor with 18F-FDG uptake (left; arrows) and image-based tumor-to-background uptake ratios (right). PET studies were performed 24 h after treatment with resveratrol and again 24 h after vehicle injection (top) or in reverse sequence (bottom). Animals received single dose (A; n = 2 per group) or 2 doses of resveratrol and vehicle (B; n = 4 or 5 per group) in opposite sequences. Bars are mean ± SD of uptake ratios. n.s. = not significant.
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