Inhibition of fos-jun-DNA complex formation by dihydroguaiaretic acid and in vitro cytotoxic effects on cancer cells.
The effect of dihydroguaiaretic acid (DHGA), isolated from the aryls of Myristica fragrans, on the transcription factor (fos-jun dimer) action was investigated via in vitro assay. DHGA showed an inhibitory effect against the complex formation of the fos-jun dimer and the DNA consensus sequence with an IC50 value of 0.21 micromol. Nordihydroguaiaretic acid (NDGA) and curcumin also inhibited fos-jun dimer action showing IC50 values of 7.9 and 6.9 nmol, respectively. DHGA and NDGA suppressed leukemia, lung cancer and colon cancer in an in vitro bioassay. The in vitro experiment suggested that inhibition of fos-jun-DNA complex formation could be due to the direct interference of fos-jun dimer binding onto the DNA consensus sequence by NDGA and curcumin.
Park
S
S
Department of Chemistry, Seoul National University, South Korea.
Lee
D K
DK
Yang
C H
CH
D019281:Dimerization; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects*; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017705:Lignans; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C015816:dihydroguaiaretic acid; D006139:Guaiacol; D009637:Masoprocol