title: Apoptotic effect of dibenzylideneacetone on oral cancer cells via modulation of specificity protein 1 and Bax.
abstract: OBJECTIVE
  Dibenzylideneacetone (DBA), an analogue of curcumin, has been shown to have potential anticancer effects against several cancers. However, the molecular mechanism underlying anticancer activity of DBA has not been well established yet. In this study, we investigated the function and molecular mechanism of DBA in human oral cancer cells.
  
  
  METHODS
  The growth-inhibitory and apoptotic effects and related signaling pathways of DBA were evaluated using trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole staining, Western blot analysis, siRNA, and reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  DBA inhibited cell growth and induced apoptosis, as evidenced by PARP cleavage, activation of caspase-3, and nuclear condensation. DBA also decreased specificity protein 1 (Sp1) expression through facilitating protein degradation. In addition, DBA enhanced the induction of pro-apoptotic protein Bax, resulting in their conformational change, translocation into mitochondrial outer membrane, and its oligomerization. The down-regulation of Sp1 by siRNA targeting Sp1 and mithramycin A increasingly activated Bax to trigger apoptosis. Moreover, DBA-induced growth inhibition and apoptosis in various human oral cancer cell lines were associated with Sp1 down-regulation and induction of Bax.
  
  
  CONCLUSIONS
  These findings suggest that DBA may be a potential anticancer drug candidate to induce apoptosis through down-regulation of Sp1 in human oral cancer.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Yu
authors.forename: J A
authors.initials: JA
authors.lastname: Shin
authors.forename: J S
authors.initials: JS
authors.lastname: Nam
authors.forename: B S
authors.initials: BS
authors.lastname: Kang
authors.forename: S D
authors.initials: SD
authors.lastname: Cho
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015536:Down-Regulation; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology*; D010422:Pentanones / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000187:drug effects* / Q000502:physiology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000187:drug effects* / Q000502:physiology*
chemical_list: D010422:Pentanones; D016329:Sp1 Transcription Factor; D051028:bcl-2-Associated X Protein; C533260:dibenzylidene acetone
keywords: Bax; apoptosis; dibenzylideneacetone; oral cancer; specificity protein 1