title: Colchicine derivative as a potential anti-glioma compound.
abstract: Colchicine, an anti-microtubule and antimitotic drug, is a common therapeutically agent for gout, which is thought to have potential anti-tumor effects. Owing to concerns of colchicines poisoning, the development of derivatives with low dose efficacy and less side effects is of obvious interest. In this study, we characterized the inhibitory effects of a colchicine derivative named AD1 on the cell proliferation of human malignant glioblastoma (MG) cell lines, U87MG and U373MG. We found that 50 % of U87MG and U373MG cells were reduced in the cultures after exposure to AD1 for 24 h at 10 and 50 nM, respectively. Moreover, α-tubulin immunostaining indicated that AD1 induced the disruption of the microtubule polymerization in glioma cells with apoptotic features including membrane budding/blebbing or fragmented nuclei. Increased levels of reactive oxygen species (ROS) were also detected in AD1-treated U87MG and U373MG cells compared to that observed in the control culture. Moreover, examination of microtubule-associated protein 1A/1B-light chain 3 (LC3I)/LC3II conversion and acridine orange staining for autophagic vesicles, combined with flow cytometry, showed that treatment with AD1 induced the autophagic pathway in U87MG and U373MG cells. Furthermore, we found that the intermittent intravenous administration of AD1 suppressed glioma growth in rat brain receiving intracerebral injection with rat C6 glioma cells. Taken together, our findings reveal that treatment with AD1 at nanomolar scales can reduce glioma cell viability effectively, with the occurrence of a rise in ROS and cellular autophagy. In conjunction with the observations from in vivo study, the colchicine derivative AD1 has chemotherapeutic potential to suppress glioma progression.
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Kuan-Min
authors.initials: KM
authors.lastname: Fang
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: Jun-Jen
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.|Center for Cell Dynamics, Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Chun-Chun
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Chih-Chi
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Yun-Ti
authors.initials: YT
authors.lastname: Hsieh
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Kit Man
authors.initials: KM
authors.lastname: Chai
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC.
authors.forename: Yu-An
authors.initials: YA
authors.lastname: Lien
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan, ROC. stzeng@mail.ncku.edu.tw.|Center for Cell Dynamics, Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan, ROC. stzeng@mail.ncku.edu.tw.|Department of Life Sciences, National Cheng Kung University, #1 University Road, Tainan City, 70101, Taiwan, ROC. stzeng@mail.ncku.edu.tw.
authors.forename: Shun-Fen
authors.initials: SF
authors.lastname: Tzeng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D014404:Tubulin; D003078:Colchicine
keywords: AD1; Acidic vesicular organelles; Autophagy; Colchicine; Glioma