title: (2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide induces apoptosis and cell cycle arrest in HL-60 cells.
abstract: BACKGROUND
  Ferulic acid is one of the most ubiquitous phenolic compounds in nature, which has antioxidant and anticancer activities. However, ferulic acid derivatives, such as ferulamide have never been reported.
  
  
  METHODS
  (2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide (compound 8), a ferulamide derivative was synthesized in our laboratory. In this study, HL-60 cells were treated with various concentrations of compound 8, and its effects on cell growth, cell cycle, apoptosis and related measurements were investigated.
  
  
  RESULTS
  Compound 8 inhibited cell growth in a concentration- and time-dependent manner with significant cytotoxicity, and the concentration required to inhibit growth by 50% (IC50) was 8.2 microM for 24 h. The cell cycle analysis indicated that compound 8 treated cells were arrested in the G2/M-phase and followed by apoptosis. Microscopic examination showed that treatment with compound 8 displayed typical morphological features of apoptotic cells, with cell shrinking and formation of apoptotic bodies. Reverse transcription-polymerase chain reaction (RT- PCR) analysis showed a dramatic induction of CDK inhibitor p21, which inhibited the expression of cyclin B1, thereby resulting in G2/M phase arrest. After G2/M-phase arrest, cells underwent apoptosis via significant down-regulation of Bcl-2 expression.
  
  
  CONCLUSIONS
  These results enhance our understanding of the mechanisms of action of compound 8-mediated anticancer effects.
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, ROC.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Hsu
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Ya-Yun
authors.initials: YY
authors.lastname: Lai
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
authors.forename: Li-Jiau
authors.initials: LJ
authors.lastname: Huang
mesh_terms: D000178:Acrylamides / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C518368:(2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide; D000178:Acrylamides; D000970:Antineoplastic Agents; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein