title: A potent anticancer agent of shikonin derivative targeting tubulin.
abstract: In this study, a shikonin ester derivative, compound , was selected to evaluate its anticancer activities and we found that compound exhibited better antitubulin activities against the human HepG2 cell line with an IC50 value of 1.097 μM. Furthermore, the inhibition of tubulin polymerization results indicated that compound demonstrated the most potent antitubulin activity (IC50  = 13.88), which was compared with shikonin and colchicine as positive controls (IC50  = 25.28 μM and 22.56 μM), respectively. Compound was simulated to have good binding site with tubulin and arrested the cell cycle at G2/M phase, which also induces apoptosis in HepG2 cells, in which P53 and members of Bcl-2 protein family were both involved in the progress of apoptosis revealed by western blot. Confocal microscopy observations revealed compound targeted tubulin and altered its polymerization by interfering with microtubule organization. Based on these results, compound functions as a potent anticancer agent targeting tubulin.
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P.R. China; Department of Biotechnology, FCPD, Sindh Agriculture University, Tandojam, Pakistan.
authors: Shahla Karim
authors: SK
authors: Baloch
authors: Lin
authors: L
authors: Ma
authors: Guo-Hua
authors: GH
authors: Xu
authors: Li-Fei
authors: LF
authors: Bai
authors: Hua
authors: H
authors: Zhao
authors: Cheng-Yi
authors: CY
authors: Tang
authors: Yan-Jun
authors: YJ
authors: Pang
authors: Rong-Wu
authors: RW
authors: Yang
authors: Xiao-Ming
authors: XM
authors: Wang
authors: Gui-Hua
authors: GH
authors: Lu
authors: Yong-Hua
authors: YH
authors: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects; D062105:Molecular Docking Simulation; D009285:Naphthoquinones / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D050257:Tubulin Modulators; C016101:shikonin
keywords: anticancer; antitubulin; shikonin derivative