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.
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.
Park
Jong Kuk
JK
Brain Korea 21 Biomedical Sciences, College of Medicine, Korea University, Seoul, Korea.
Chung
Young Min
YM
Kim
Byung-Gyu
BG
Yoo
Young-A
YA
Yang
Beom-Seok
BS
Kim
Jun Suk
JS
Yoo
Young Do
YD
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000532:radiotherapy*; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects* / Q000528:radiation effects*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005720:Gamma Rays / Q000627:therapeutic use; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097642:GADD45 Proteins
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D006835:Hydrazones; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; D013859:Thiocarbamates; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D048051:p38 Mitogen-Activated Protein Kinases; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C499072:Gadd45a protein, mouse; C493162:N'-(phenylpyridin-2-ylmethylene)hydrazine carbodithioic acid methyl ester