title: Induction of S-Phase Arrest in Human Glioma Cells by Selenocysteine, a Natural Selenium-Containing Agent Via Triggering Reactive Oxygen Species-Mediated DNA Damage and Modulating MAPKs and AKT Pathways.
abstract: Selenocysteine (SeC) a natural available selenoamino acid exhibits novel anticancer activities against human cancer cell lines. However, the growth inhibitory effect and mechanism of SeC in human glioma cells remain unclear. The present study reveals that SeC time- and dose-dependently inhibited U251 and U87 human glioma cells growth by induction of S-phase cell cycle arrest, followed by the marked decrease of cyclin A. SeC-induced S-phase arrest was achieved by inducing DNA damage through triggering generation of reactive oxygen species (ROS) and superoxide anion, with concomitant increase of TUNEL-positive cells and induction of p21waf1/Cip1 and p53. SeC treatment also caused the activation of p38MAPK, JNK and ERK, and inactivation of AKT. Four inhibitors of MAPKs and AKT pathways further confirmed their roles in SeC-induced S-phase arrest in human glioma cells. Our findings advance the understanding on the molecular mechanisms of SeC in human glioma management.
authors: Department of Neurology, Shandong University School of Medicine, Jinan, 250012, Shandong, China.|Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Kun
authors: K
authors: Wang
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Xiao-Ting
authors: XT
authors: Fu
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Yuan
authors: Y
authors: Li
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Ya-Jun
authors: YJ
authors: Hou
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Ming-Feng
authors: MF
authors: Yang
authors: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Jing-Yi
authors: JY
authors: Sun
authors: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China.
authors: Shu-Ying
authors: SY
authors: Yi
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. tcdfan66@163.com.
authors: Cun-Dong
authors: CD
authors: Fan
authors: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China. fxy007800@163.com.
authors: Xiao-Yan
authors: XY
authors: Fu
authors: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China. jingzhai66@163.com.
authors: Jing
authors: J
authors: Zhai
authors: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. blsun88@163.com.|Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, China. blsun88@163.com.
authors: Bao-Liang
authors: BL
authors: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004249:DNA Damage / Q000502:physiology*; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology; D017279:Selenocysteine / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D017279:Selenocysteine; D051058:Oncogene Protein v-akt; D012643:Selenium
keywords: AKT; Cell cycle arrest; DNA damage; Glioma; MAPKs; Reactive oxygen species; Selenocysteine