title: Induction of G1 Cell Cycle Arrest in Human Glioma Cells by Salinomycin Through Triggering ROS-Mediated DNA Damage In Vitro and In Vivo.
abstract: Chemotherapy has always been one of the most effective ways in combating human glioma. However, the high metastatic potential and resistance toward standard chemotherapy severely hindered the chemotherapy outcomes. Hence, searching effective chemotherapy drugs and clarifying its mechanism are of great significance. Salinomycin an antibiotic shows novel anticancer potential against several human tumors, including human glioma, but its mechanism against human glioma cells has not been fully elucidated. In the present study, we demonstrated that salinomycin treatment time- and dose-dependently inhibited U251 and U87 cells growth. Mechanically, salinomycin-induced cell growth inhibition against human glioma was mainly achieved by induction of G1-phase arrest via triggering reactive oxide species (ROS)-mediated DNA damage, as convinced by the activation of histone, p53, p21 and p27. Furthermore, inhibition of ROS accumulation effectively attenuated salinomycin-induced DNA damage and G1 cell cycle arrest, and eventually reversed salinomycin-induced cytotoxicity. Importantly, salinomycin treatment also significantly inhibited the U251 tumor xenograft growth in vivo through triggering DNA damage-mediated cell cycle arrest with involvement of inhibiting cell proliferation and angiogenesis. The results above validated the potential of salinomycin-based chemotherapy against human glioma.
authors.affiliation: Department of Neurology, Shandong University School of Medicine, Jinan, Shandong, 250012, China.|Taishan Medical University, Taian, Shandong, 271000, China.|Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, 014040, China.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi, Shandong, 276000, China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Qing-Jian
authors.initials: QJ
authors.lastname: Wu
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Fu
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Lu-Rong
authors.initials: LR
authors.lastname: Shao
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Sun
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China. blsun88@163.com.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Sun
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China. jingzhai66@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhai
authors.affiliation: Taishan Medical University, Taian, Shandong, 271000, China. tcdfan66@163.com.
authors.forename: Cun-Dong
authors.initials: CD
authors.lastname: Fan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011714:Pyrans / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000095662:Polyether Polyketides
chemical_list: D011714:Pyrans; D017382:Reactive Oxygen Species; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Cell cycle arrest; DNA damage; Glioma; Reactive oxide species; Salinomycin