title: Curcumin induces G2/M arrest and triggers apoptosis via FoxO1 signaling in U87 human glioma cells.
abstract: It has previously been demonstrated that curcumin possesses an antitumor activity, which is associated with its ability to induce G2/M cell cycle arrest and apoptosis. However the detailed underlying mechanisms remain unclear. The present study aimed to investigate the efficacy and underlying mechanism of curcumin‑induced cell cycle arrest and apoptosis in U87 human glioblastoma cells. By immunofluorescence staining, subcellular fractionation and western blotting, the present study demonstrated that curcumin was able to induce G2/M cell cycle arrest and apoptosis by increasing the expression levels of cyclin G2, cleaved caspase‑3 and Fas ligand (FasL), and decreasing the expression of cyclin‑dependent kinase 1 (CDK1). In addition, increased expression of forkhead box protein O1 (FoxO1) and decreased expression of phosphorylated (p)‑FoxO1 were detected in the curcumin‑treated U87 cells. Curcumin was also able to induce the translocation of FoxO1 from the cytoplasm to the nucleus. Furthermore, following knockdown of FoxO1 expression in curcumin‑treated U87 cells using FoxO1 small interfering RNA, the expression levels of cyclin G2, cleaved caspase‑3 and FasL were inhibited; however, the expression levels of CDK1 were not markedly altered. Notably, following knockdown of CDK1 expression under normal conditions, the total expression of FoxO1 was not affected; however, p‑FoxO1 expression was decreased and FoxO1 nuclear expression was increased. Furthermore, curcumin‑induced G2/M cell cycle arrest and apoptosis could be attenuated by FoxO1 knockdown. These results indicated that curcumin may induce G2/M cell cycle arrest and apoptosis in U87 cells by increasing FoxO1 expression. The present study identified a novel mechanism underlying the antitumor effects of curcumin, and may provide a theoretical basis for the application of curcumin in glioma treatment.
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Jian-Tong
authors.initials: JT
authors.lastname: Jiao
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Min-Chao
authors.initials: MC
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Zong
authors.affiliation: Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China.
authors.forename: Jun-Fei
authors.initials: JF
authors.lastname: Shao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D000071161:Forkhead Box Protein O1 / Q000096:biosynthesis*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D009363:Neoplasm Proteins; D003474:Curcumin