title: Effects of curcumin on cancer cell mitochondrial function and potential monitoring with ¹⁸F-FDG uptake.
abstract: A better understanding of how curcumin influences cancer cell biology could help devise new strategies to enhance its antitumor effect. Many curcumin actions are proposed to occur by targeting mitochondrial function, among which glucose metabolism and reactive oxygen species (ROS) production are pivotal. However, little is known of how curcumin influences cancer cell glucose metabolism. We thus evaluated the effect of curcumin on cancer cell glucose metabolism and mitochondrial function, and further investigated whether these responses could be modified to enhance the anticancer potency of the compound. MCF-7 breast cancer cells treated with curcumin were measured for 18F-fluorodeoxyglucose (18F‑FDG) uptake, lactate production, hexokinase activity, oxygen consumption rate (OCR), ROS production and mitochondrial membrane potential (MMP). Activation of signaling pathways was evaluated by western blots, and cell survival was assessed with sulforhodamine B assays. Curcumin stimulated a 3.6-fold increase of 18F-FDG uptake in MCF-7 cells, along with augmented hexokinase activity and lactate efflux. This was accompanied by significantly suppressed cellular OCR, consistent with a metabolic shift to glycolytic flux. Inhibiting this metabolic response with 2-deoxyglucose (2-DG) blocked curcumin-induced mTOR activation and resulted in a greater anti-proliferative effect. Curcumin-induced MMP depolarization led to reduced ROS production, which may hinder the anticancer effect of the compound. Intracellular ROS was completely restored by adding Cu2+, which can bind and modify the curcumin's physico-chemical property, and this resulted in a marked potentiation of its anti-proliferative effect. Thus, curcumin suppresses cancer cell MMP and ROS generation, and this response is accompanied by stimulated 18F-FDG uptake via shifting of metabolism from mitochondrial respiration to glycolytic flux. These mitochondrial and metabolic responses may provide potential targets that can help enhance the anticancer action of curcumin.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000000981:diagnostic imaging / Q000187:drug effects*; D009369:Neoplasms / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D017382:Reactive Oxygen Species; D019788:Fluorodeoxyglucose F18; D003474:Curcumin