title: Caffeine-induced nuclear translocation of FoxO1 triggers Bim-mediated apoptosis in human glioblastoma cells.
abstract: Caffeine is one of the most commonly ingested neuroactive compounds and exhibits anticancer effects through induction of apoptosis and suppression of cell proliferation. However, the mechanisms underlying these effects are currently unknown. In this study, we investigated the mechanisms of caffeine-induced apoptosis in U251 cells (human glioma cell line). We analyzed the inhibitory effects of caffeine on cell proliferation by performing WST-8 and colony formation assays; in addition, cell survival was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometric analysis. Western blotting was used to investigate the role played by FoxO1 in the proapoptotic effects of caffeine on glioma cells. Results showed that caffeine inhibited proliferation and survival of human glioma cells, induced apoptosis, and increased the expression of FoxO1 and its proapoptotic target Bim. In addition, we found that FoxO1 enhanced the transcription of its proapoptotic target Bim. In summary, our data indicates that FoxO1-Bim mediates caffeine-induced regression of glioma growth by activating cell apoptosis, thereby providing new mechanistic insight into the possible use of caffeine in treating human cancer.
authors.affiliation: Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China.
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China.
authors.forename: Bo-Qiang
authors.initials: BQ
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. jingdehua1963@163.com.
authors.forename: De-Hua
authors.initials: DH
authors.lastname: Jiang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D000072224:Bcl-2-Like Protein 11 / Q000502:physiology*; D002110:Caffeine / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism*; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology
chemical_list: D000072224:Bcl-2-Like Protein 11; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D002110:Caffeine; D019869:Phosphatidylinositol 3-Kinases
keywords: Apoptosis; Bim; Caffeine; Forkhead box O1 (FoxO1)