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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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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.
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참고문헌 (36)
참고문헌 신청
Masamoto Y / 2003 / Mushroom tyrosinase inhibitory activity of esculetin isolated from seeds of Euphorbia lathyris L / Biosci Biotechnol Biochem 67:631~634
Payá M / 1992 / Interactions of a series of coumarins with reactive oxygen species. Scavenging of superoxide, hypochlorous acid and hydroxyl radicals / Biochem Pharmacol 44:205~214
Yang J / 2010 / Aesculetin-induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway in human cervical cancer cells / J Asian Nat Prod Res 12:185~193
Huang HC / 1993 / Antiproliferative effect of esculetin on vascular smooth muscle cells: possible roles of signal transduction pathways / Eur J Pharmacol 237:39~44
Matsunaga K / 1998 / Inhibitory effects of nabumetone, a cyclooxygenase-2 inhibitor, and esculetin, a lipoxygenase inhibitor, on N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats / Jpn J Cancer Res 89:496~501
Payá M / 1992 / Interactions of a series of coumarins with reactive oxygen species. Scavenging of superoxide, hypochlorous acid and hydroxyl radicals / Biochem Pharmacol 44:205~214
Yang J / 2010 / Aesculetin-induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway in human cervical cancer cells / J Asian Nat Prod Res 12:185~193
Huang HC / 1993 / Antiproliferative effect of esculetin on vascular smooth muscle cells: possible roles of signal transduction pathways / Eur J Pharmacol 237:39~44
Matsunaga K / 1998 / Inhibitory effects of nabumetone, a cyclooxygenase-2 inhibitor, and esculetin, a lipoxygenase inhibitor, on N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats / Jpn J Cancer Res 89:496~501
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