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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 - J Cancer Prev (2015)

Bottom Line: 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).Our results clearly demonstrated that esculetin induced apoptosis in the HMM cells by downregulating Sp1 protein levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju, Chungnam National University, Daejeon, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

The effect of esculetin on the cell viability in G361 cells. (A) Chemical structure of esculetin. (B) Cell viability effects of esculetin on G361 cells. The G361 cells were treated with esculetin (0, 10, 20, 40, and 80 μg/mL) for 24 hours and 48 hours, and the cell viabilities were measured with an MTS assay. The asterisk indicates a significant difference relative to untreated control cells (*P < 0.05). (C) Changes in the cell morphologies in G361 cells treated or untreated with esculetin (0, 20, 40, and 80 μg/mL) for 48 hours (×40).
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f1-jcp-20-106: The effect of esculetin on the cell viability in G361 cells. (A) Chemical structure of esculetin. (B) Cell viability effects of esculetin on G361 cells. The G361 cells were treated with esculetin (0, 10, 20, 40, and 80 μg/mL) for 24 hours and 48 hours, and the cell viabilities were measured with an MTS assay. The asterisk indicates a significant difference relative to untreated control cells (*P < 0.05). (C) Changes in the cell morphologies in G361 cells treated or untreated with esculetin (0, 20, 40, and 80 μg/mL) for 48 hours (×40).

Mentions: To examine the effects of esculetin (Fig. 1A) on the cell proliferation in G361 cells, we conducted MTS assay to evaluate the viability. We found that the cell viability of G361 cells was decreased at both 24 hours and 48 hours by treatment of esculetin in a dose dependent manner (Fig. 1B). When G361 HMM cells were treated with esculetin for 48 hours, the cell viability was 94%, 65%, 57%, and 34% at 10, 20, 40, and 80 μg/mL compared with a vehicle treated control group, respectively (Fig. 1B). The IC50 value on the cell viability was about 42.86 μg/mL in G361 HMM cells at 48 hours by esculetin treatment. We further observed that esculetin induced severe morphological changes including cytoplasmic blebbing, irregular cell morphology change and detachment from cell culture vessels in a dose dependent manner (Fig. 1C). These results strongly suggest that esculetin inhibits G361 HMM cells.


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 - J Cancer Prev (2015)

The effect of esculetin on the cell viability in G361 cells. (A) Chemical structure of esculetin. (B) Cell viability effects of esculetin on G361 cells. The G361 cells were treated with esculetin (0, 10, 20, 40, and 80 μg/mL) for 24 hours and 48 hours, and the cell viabilities were measured with an MTS assay. The asterisk indicates a significant difference relative to untreated control cells (*P < 0.05). (C) Changes in the cell morphologies in G361 cells treated or untreated with esculetin (0, 20, 40, and 80 μg/mL) for 48 hours (×40).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492354&req=5

f1-jcp-20-106: The effect of esculetin on the cell viability in G361 cells. (A) Chemical structure of esculetin. (B) Cell viability effects of esculetin on G361 cells. The G361 cells were treated with esculetin (0, 10, 20, 40, and 80 μg/mL) for 24 hours and 48 hours, and the cell viabilities were measured with an MTS assay. The asterisk indicates a significant difference relative to untreated control cells (*P < 0.05). (C) Changes in the cell morphologies in G361 cells treated or untreated with esculetin (0, 20, 40, and 80 μg/mL) for 48 hours (×40).
Mentions: To examine the effects of esculetin (Fig. 1A) on the cell proliferation in G361 cells, we conducted MTS assay to evaluate the viability. We found that the cell viability of G361 cells was decreased at both 24 hours and 48 hours by treatment of esculetin in a dose dependent manner (Fig. 1B). When G361 HMM cells were treated with esculetin for 48 hours, the cell viability was 94%, 65%, 57%, and 34% at 10, 20, 40, and 80 μg/mL compared with a vehicle treated control group, respectively (Fig. 1B). The IC50 value on the cell viability was about 42.86 μg/mL in G361 HMM cells at 48 hours by esculetin treatment. We further observed that esculetin induced severe morphological changes including cytoplasmic blebbing, irregular cell morphology change and detachment from cell culture vessels in a dose dependent manner (Fig. 1C). These results strongly suggest that esculetin inhibits G361 HMM cells.

Bottom Line: 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).Our results clearly demonstrated that esculetin induced apoptosis in the HMM cells by downregulating Sp1 protein levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University, Jeonju, Chungnam National University, Daejeon, Korea.

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.

No MeSH data available.


Related in: MedlinePlus