title: Caffeine inhibits cell proliferation and regulates PKA/GSK3β pathways in U87MG human glioma cells.
abstract: Caffeine is the most commonly ingested methylxanthine and has anti-cancer effects in several types of cancer. In this study, we examined the anti-cancer effects of caffeine on gliomas, both in vitro and in vivo. In vitro, caffeine treatment reduced glioma cell proliferation through G(0)/G(1)-phase cell cycle arrest by suppressing Rb phosphorylation. In addition, caffeine induced apoptosis through caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. Caffeine also phosphorylated serine 9 of glycogen synthase kinase 3 beta (GSK3β). Pretreatment with H89, a pharmacological inhibitor of protein kinase A (PKA), was able to antagonize caffeine-induced GSK3β(ser9) phosphorylation, suggesting that the mechanism might involve a cAMP-dependent PKA-dependent pathway. In vivo, caffeine-treated tumors exhibited reduced proliferation and increased apoptosis compared with vehicle-treated tumors. These results suggest that caffeine induces cell cycle arrest and caspase-dependent cell death in glioma cells, supporting its potential use in chemotherapeutic options for malignant gliomas.
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, 660-751, Korea.
authors.forename: Bo Mi
authors.initials: BM
authors.lastname: Ku
authors.forename: Yeon Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Jeong
authors.forename: Jinhyun
authors.initials: J
authors.lastname: Ryu
authors.forename: Jungil
authors.initials: J
authors.lastname: Choi
authors.forename: Joon Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Yong Woon
authors.initials: YW
authors.lastname: Cho
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007399:Interphase / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D023041:Xenograft Model Antitumor Assays
chemical_list: D002110:Caffeine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3