Induction of G1 Cell Cycle Arrest in Human Glioma Cells by Salinomycin Through Triggering ROS-Mediated DNA Damage In Vitro and In Vivo |
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Authors: | Shi-Jun Zhao Xian-Jun Wang Qing-Jian Wu Chao Liu Da-Wei Li Xiao-Ting Fu Hui-Fang Zhang Lu-Rong Shao Jing-Yi Sun Bao-Liang Sun Jing Zhai Cun-Dong Fan |
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Institution: | 1.Department of Neurology,Shandong University School of Medicine,Jinan,China;2.Taishan Medical University,Taian,China;3.Department of Neurology,Baotou Central Hospital,Baotou,China;4.Department of Neurology,Linyi People’s Hospital,Linyi,China |
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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. |
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