Trans-4-lodo,4'-boranyl-chalcone induces antitumor activity against malignant glioma cell lines in vitro and in vivo.
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.
Sasayama
Takashi
T
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
Tanaka
Kazuhiro
K
Mizukawa
Katsu
K
Kawamura
Atsufumi
A
Kondoh
Takeshi
T
Hosoda
Kohkichi
K
Kohmura
Eiji
E
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
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