CD133 increases oxidative glucose metabolism of HT29 cancer cells by mitochondrial uncoupling and its inhibition enhances reactive oxygen species-inducing therapy. Issue 8 (30th May 2022)

• Record Type: Journal Article
• Authors: Lee, Jin Hee; Lee, Eun Ji; Park, Jin Won; Kim, Mina; Jung, Kyung-Ho; Cho, Young Seok; Lee, Kyung-Han
• Is Part Of: Nuclear medicine communications. Volume 43:Issue 8(2022)
• Page Start: 937
• Page End: 944
• Publication Date: 2022-05-30
• Subjects: CD133 -- colon cancer -- glucose -- oxygen consumption rate -- mitochondrial reactive oxygen species; Nuclear medicine -- Periodicals; 616.07575
• DOI: 10.1097/MNM.0000000000001587
• Languages: English
• ISSNs: 0143-3636

Abstract

Abstract : Objective: A better understanding of the metabolic phenotype of stem-like cancer cells could provide targets to help overcome chemoresistance. In this study, we hypothesized that colon cancer cells with the stem cell feature of CD133 expression have increased proton leakage that influences glucose metabolism and offers protection against reactive oxygen species (ROS)-inducing treatment. Methods and Results: In HT29 colon cancer cells, 18 F-fluorodeoxyglucose (FDG) uptake was increased by CD133 selection and decreased by CD133 silencing. In CD133(+) cells, greater 18 F-FDG uptake was accompanied by increased oxygen consumption rate (OCR) and reduced mitochondrial membrane potential and mitochondrial ROS, indicating increased proton leakage. The uncoupling protein inhibitor genipin reversed the increased 18 F-FDG uptake and greater OCR of CD133(+) cells. The ROS-inducing drug, piperlongumine, suppressed CD133(−) cell survival by stimulating mitochondrial ROS generation but was unable to influence CD133(+) cells when used alone. However, cotreatment of CD133(+) cells with genipin and piperlongumine efficiently stimulated mitochondrial ROS for an enhanced antitumor effect with substantially reduced CD133 expression. Conclusion: These results demonstrate that mitochondrial uncoupling is a metabolic feature of CD133(+) colon cancer cells that provides protection against piperlongumine therapy by suppressing mitochondrial ROS generation. Hence, combining genipin with ROS-inducing treatment may be an effective strategy to reverse the metabolic feature and eliminate stem-like colon cancer cells.