title: LJNK, an indoline-2,3-dione-based aminopeptidase N inhibitor with promising antitumor potency.
abstract: In our previous study, we found that LJNK showed potent aminopeptidase N (APN)-inhibitory activity. In the current study, we further evaluated the antitumor effects of LJNK both in vitro and in vivo. Enzyme experiments showed that LJNK showed better inhibitory activity than bestatin against APN both from human carcinoma cells' surface and from porcine kidney microsomes. In addition, LJNK could suppress rat aortic ring microvessel growth and HUVEC tubular structure formation, which showed its stronger antiangiogenesis effects than bestatin. [(3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide)] assay and clonogenic assay showed that LJNK suppressed cancer cell growth both in the short and the long term. Mice bearing H22 transplantation tumor proved its antitumor effects in vivo. Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that LJNK could induce 28.1% PLC/PRF/5 cell apoptosis and the apoptotic pathway was probably identified by western blot. The above-mentioned results suggested that LJNK inhibited cell proliferation and angiogenesis, and induced apoptosis by decreasing APN activity.
authors.affiliation: aDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan bKey Laboratory of Applied Pharmacology in Shandong Province, Department of Pharmacology, School of Pharmacy, Weifang Medical College cBochuang International Medical Institute, Weifang, Shandong, People's Republic of China.
authors.forename: Jinning
authors.initials: J
authors.lastname: Hou
authors.forename: Kang
authors.initials: K
authors.lastname: Jin
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Li
authors.forename: Xuejian
authors.initials: X
authors.lastname: Wang
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Huang
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D055806:Microvessels / Q000187:drug effects; D062105:Molecular Docking Simulation; D051381:Rats; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C000625739:LJNK compound; D007510:Isatin; D018826:CD13 Antigens