J Cancer Prev.  2015 Jun;20(2):106-112. 10.15430/JCP.2015.20.2.106.

Esculetin, a Coumarin Derivative, Exhibits Anti-proliferative and Pro-apoptotic Activity in G361 Human Malignant Melanoma

• Jeon YJ
• Jang JY
• Shim JH
• Myung PK
• Chae JI

• KMID: 2171335
• DOI: http://doi.org/10.15430/JCP.2015.20.2.106

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.

Keyword

Esculetin; Apoptosis; Melanoma; Sp1 transcription factor

MeSH Terms

Apoptosis
Blotting, Western
Caspase 3
Cell Death
Cyclin D1
Humans*
Melanoma*
Sp1 Transcription Factor
Caspase 3
Cyclin D1
Sp1 Transcription Factor