title: Esculetin, a Coumarin Derivative, Exhibits Anti-proliferative and Pro-apoptotic Activity in G361 Human Malignant Melanoma.
abstract: BACKGROUND
  Although esculetin, a coumarin compound, is known to induce apoptosis in human cancer cells, the effects and molecular mechanisms on the apoptosis in human malignant melanoma (HMM) cells are not well understood yet. In this study, we investigated the anti-proliferative effects of esculetin on the G361 HMM cells.
  
  
  METHODS
  We analyzed the anti-proliferative effects and molecular mechanisms of esculetin on G361 cells by a 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, 4',6-diamidino-2-phenylindole staining and Western blotting.
  
  
  RESULTS
  Esculetin exhibited significant anti-proliferative effects on the HMM cells in a dose-dependent manner. Interestingly, we found that esculetin induced nuclear shrinkage and fragmentation, typical apoptosis markers, by suppression of Sp1 transcription factor (Sp1). Notably, esculetin modulated Sp1 downstream target genes including p27, p21 and cyclin D1, resulted in activation of apoptosis signaling molecules such as caspase-3 and PARP in G361 HMM cells.
  
  
  CONCLUSIONS
  Our results clearly demonstrated that esculetin induced apoptosis in the HMM cells by downregulating Sp1 protein levels. Thus, we suggest that esculetin may be a potential anti-proliferative agent that induces apoptotic cell death in G361 HMM cells.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju, Chungnam National University, Daejeon, Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju, Chungnam National University, Daejeon, Korea.
authors.forename: Jeong-Yun
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan, Chungnam National University, Daejeon, Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: Pyung Keun
authors.initials: PK
authors.lastname: Myung
authors.affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju, Chungnam National University, Daejeon, Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
keywords: Apoptosis; Esculetin; Melanoma; Sp1 transcription factor