N'-(phenyl-pyridin-2-yl-methylene)-hydrazine carbodithioic acid methyl ester enhances radiation-induced cell death by targeting Bcl-2 against human lung carcinoma cells

Mol Cancer Ther. 2004 Apr;3(4):403-7.

Abstract

To develop a new radiosensitizer, we screened a chemical library and selected one chemical reagent, N'-(phenyl-pyridin-2-yl-methylene)-hydrazine carbodithioic acid methyl ester (PHCM), which was already known to have antifungal and antimicrobial properties. PHCM enhanced radiation-induced cell death and its mean calculated dose enhancement ratio was 1.17. PHCM was found to induce the phosphorylation of p38 mitogen-activated protein kinase, and combined treatment with PHCM and radiation down-regulated Bcl-2. In a xenograft assay, the combined PHCM and radiation group showed 39.3 days of growth delay versus the control in terms of tumor growth. The enhancement factor of this combined treatment was determined to be 4.02.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Cell Cycle Proteins / metabolism
  • Cell Death / drug effects*
  • Cell Death / radiation effects*
  • Cell Division / drug effects
  • Cell Division / radiation effects
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Gamma Rays / therapeutic use
  • Humans
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Hydrazones / toxicity
  • Mice
  • Nuclear Proteins / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / pharmacology*
  • Radiation-Sensitizing Agents / therapeutic use
  • Thiocarbamates / chemistry
  • Thiocarbamates / pharmacology*
  • Thiocarbamates / toxicity
  • Tumor Suppressor Protein p53 / metabolism
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • GADD45A protein, human
  • Gadd45a protein, mouse
  • Hydrazones
  • N'-(phenylpyridin-2-ylmethylene)hydrazine carbodithioic acid methyl ester
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Radiation-Sensitizing Agents
  • Thiocarbamates
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • p38 Mitogen-Activated Protein Kinases