title: Combination treatment with fasudil and clioquinol produces synergistic anti-tumor effects in U87 glioblastoma cells by activating apoptosis and autophagy.
abstract: Survival of patients with glioblastoma (GBM) remains poor, and novel treatment methods are urgently needed. In this study, we tested the effects of a combination of fasudil, a ROCK inhibitor, and clioquinol, an 8-hydroxyquinoline derivative with antimicrobial properties, on human GBM U87 cells. Combination treatment synergistically inhibited the viability of glioma cells but not mouse normal neuron HT22 cells and significantly induced mitochondria-mediated apoptosis. Moreover, the combination was also found to trigger macro-autophagy (henceforth referred to as autophagy) by increasing the expression levels of several proteins involved in the induction of autophagy. Further studies showed that 3-methyladenine (3-MA) or chloroquine (CQ), two autophagy inhibitors, abrogated the cytotoxic effects of the combination treatment as well as the autophagy. Overall, we demonstrated that fasudil and clioquinol show synergistic anti-cancer effects, providing evidence for the further development of combination therapy for GBM.
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciecnes, Sun Yat-Sen University, Guangzhou, 510006, China.
authors.forename: Jingkao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Kaishu
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Meiguang
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Yinlun
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Leping
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People's Republic of China. liuanmin@mail.sysu.edu.cn.
authors.forename: Anmin
authors.initials: A
authors.lastname: Liu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D007464:Clioquinol / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D005909:Glioblastoma; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D047428:Protein Kinase Inhibitors; D007464:Clioquinol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil
keywords: Apoptosis; Autophagy; Clioquinol; Fasudil; Glioblastoma; Synergistic effect