title: Resveratrol Induces Glioma Cell Apoptosis through Activation of Tristetraprolin.
abstract: Tristetraprolin (TTP) is an AU-rich elements (AREs)-binding protein, which regulates the decay of AREs-containing mRNAs such as proto-oncogenes, anti-apoptotic genes and immune regulatory genes. Despite the low expression of TTP in various human cancers, the mechanism involving suppressed expression of TTP is not fully understood. Here, we demonstrate that Resveratrol (3,5,4'-trihydroxystilbene, Res), a naturally occurring compound, induces glioma cell apoptosis through activation of tristetraprolin (TTP). Res increased TTP expression in U87MG human glioma cells. Res-induced TTP destabilized the urokinase plasminogen activator and urokinase plasminogen activator receptor mRNAs by binding to the ARE regions containing the 3' untranslated regions of their mRNAs. Furthermore, TTP induced by Res suppressed cell growth and induced apoptosis in the human glioma cells. Because of its regulation of TTP expression, these findings suggest that the bioactive dietary compound Res can be used as a novel anti-cancer agent for the treatment of human malignant gliomas.
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Jinhyun
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Nal Ae
authors.initials: NA
authors.lastname: Yoon
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Seong
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Seokmin
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Physiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Nammi
authors.initials: N
authors.lastname: Park
authors.affiliation: Gyeongnam Department of Environmental Toxicology and Chemistry, Korea Institute of Toxicology (KIT), Jinju 660-844, Korea.
authors.forename: Jungil
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 52727, Korea.
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
mesh_terms: D020413:3' Untranslated Regions; D063307:AU Rich Elements; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D051816:Tristetraprolin / Q000378:metabolism*; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D013267:Stilbenes; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D014568:Urokinase-Type Plasminogen Activator; D000077185:Resveratrol
keywords: TTP; apoptosis; glioma; resveratrol; uPA; uPAR