Trans-4-lodo,4'-boranyl-chalcone induces antitumor activity against malignant glioma cell lines in vitro and in vivo

J Neurooncol. 2007 Nov;85(2):123-32. doi: 10.1007/s11060-007-9395-2. Epub 2007 May 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Boron Compounds / pharmacology*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Caspases / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Chalcones / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Mice, Nude
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Statistics, Nonparametric
  • Tumor Suppressor Protein p53 / drug effects
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / drug effects

Substances

  • 4-iodo-4'-boranylchalcone
  • Antineoplastic Agents
  • Boron Compounds
  • Chalcones
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Caspases