Resveratrol Suppresses Cancer Cell Glucose Uptake by Targeting Reactive Oxygen Species–Mediated Hypoxia-Inducible Factor-1α Activation

• DOI: 10.2967/jnumed.112.115436
• Publication Date: 2013-11-13T03:01:24Z
• Authors: Kyung-Ho Jung; Jin Hee Lee; Cung Hoa Thien Quach; Jin-Young Paik; Hyunhee Oh; Jin Won Park; Eun Jeong Lee; Seung-Hwan Moon; Kyung-Han Lee
• Keywords: Lewis lung carcinoma

Resveratrol is gaining attention for its anticancer effects and also recognized antioxidant properties influence on glucose metabolism. Augmented reactive oxygen species (ROS) high glycolytic flux are common characteristics of malignant cells. We thus evaluated the effect resveratrol cancer cell metabolism investigated role ROS in response. <b>Methods:</b> Cancer cells were measured content ¹⁸F-FDG uptake. Assays performed lactate production; hexokinase activity intracellular ROS; immunoblotting hypoxia-inducible factor-1α (HIF-1α), Akt, mammalian target rapamycin, transporter type 1 (Glut-1). Animal studies with small-animal PET imaging Lewis lung carcinoma tumor–bearing mice. <b>Results:</b> mildly decreased more pronouncedly suppressed uptake carcinoma, HT-29 colon, T47D breast Hence, normalized to was reduced less than half controls by 24-h exposure resveratrol. This reduction attributed Glut-1 expression. patterns that closely paralleled Scavenging <i>N</i>-acetyl cysteine, but not inhibition nicotinamide adenine dinucleotide phosphate oxidase, sufficient suppress Conversely, inducers effectively reversed metabolic response HIF-1α protein markedly resveratrol, inhibiting expression cycloheximide or specific small interfering RNAs The proteosomal inhibitor MG132 partly restored level resveratrol-treated inhibited Akt activation; addition, inhibitors against phosphoinositide 3-kinase Finally, results showed treatment tumor vivo. <b>Conclusion:</b> suppresses a manner depends capacity inhibit ROS, which downregulates accumulation.