title: Trans-4-lodo,4'-boranyl-chalcone induces antitumor activity against malignant glioma cell lines in vitro and in vivo.
abstract: Chalcones are considered the precursors of flavonoids and have been identified as interesting compounds with antitumor properties. Boronic-chalcone derivatives are more toxic to breast cancer cells compared to normal breast cells. Here, we studied the antitumor activities of trans-4-lodo,4'-boranyl-chalcone (TLBC), which is a boronic-chalcone derivative, in several glioma cell lines. TLBC showed a dose-dependent inhibition with inhibitory concentration 50% value in the muM range (5.5-25.5 microM) in various glioma cell lines. Flow cytometric and western blot assay demonstrated that TLBC induced apoptosis independent of changes to the tumor suppressor p53. This cytotoxic effect was the caspase-dependent manner. Also, TLBC lowered levels of anti-apoptotic Bcl-2 and/or Bcl-X(L) protein in several of the cell lines. To examine the antitumor effect of TLBC in vivo, we used a malignant glioma xenograft model. This result showed that in the mice treated with TLBC at 20 mg/kg, mean tumor volume was reduced by 43.9% (P < 0.01) in comparison with the control group. Immunohistochemical and western blot analysis showed that Bcl-2 protein levels were decreased and Bax protein levels were slightly increased in the tumors injected with 20 mg/kg TLBC compared with the control tumors. Therefore, we conclude that TLBC may be a potential chemotherapeutic agent for human glioma.
authors.affiliation: Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. takasasa@med.kobe-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasayama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Katsu
authors.initials: K
authors.lastname: Mizukawa
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondoh
authors.forename: Kohkichi
authors.initials: K
authors.lastname: Hosoda
authors.forename: Eiji
authors.initials: E
authors.lastname: Kohmura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001896:Boron Compounds / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D018709:Statistics, Nonparametric; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000187:drug effects
chemical_list: C526921:4-iodo-4'-boranylchalcone; D000970:Antineoplastic Agents; D001896:Boron Compounds; D047188:Chalcones; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D020169:Caspases