Silvestrol induces early autophagy and apoptosis in human melanoma cells

BMC Cancer

Research Article

Joanna E. Burdette¹  Wei-Lun Chen¹  Steven M. Swanson²  Li Pan³  A. Douglas Kinghorn³ 

[1] Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 60607, Chicago, IL, USA;Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 60607, Chicago, IL, USA;School of Pharmacy, University of Wisconsin-Madison, 53705, Madison, WI, USA;Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, 43210, Columbus, OH, USA;

关键词: Melanoma;    Silvestrol;    Autophagy;    Apoptosis;   

DOI  :  10.1186/s12885-015-1988-0

 received in 2015-06-08, accepted in 2015-12-08,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundSilvestrol is a cyclopenta[b]benzofuran that was isolated from the fruits and twigs of Aglaia foveolata, a plant indigenous to Borneo in Southeast Asia. The purpose of the current study was to determine if inhibition of protein synthesis caused by silvestrol triggers autophagy and apoptosis in cultured human cancer cells derived from solid tumors.MethodsIn vitro cell viability, flow cytometry, fluorescence microscopy, qPCR and immunoblot was used to study the mechanism of action of silvestrol in MDA-MB-435 melanoma cells.ResultsBy 24 h, a decrease in cyclin B and cyclin D expression was observed in silvestrol-treated cells relative to control. In addition, silvestrol blocked progression through the cell cycle at the G2-phase. In silvestrol-treated cells, DAPI staining of nuclear chromatin displayed nucleosomal fragments. Annexin V staining demonstrated an increase in apoptotic cells after silvestrol treatment. Silvestrol induced caspase-3 activation and apoptotic cell death in a time- and dose-dependent manner. Furthermore, both silvestrol and SAHA enhanced autophagosome formation in MDA-MB-435 cells. MDA-MB-435 cells responded to silvestrol treatment with accumulation of LC3-II and time-dependent p62 degradation. Bafilomycin A, an autophagy inhibitor, resulted in the accumulation of LC3 in cells treated with silvestrol. Silvestrol-mediated cell death was attenuated in ATG7-null mouse embryonic fibroblasts (MEFs) lacking a functional autophagy protein.ConclusionsSilvestrol potently inhibits cell growth and induces cell death in human melanoma cells through induction of early autophagy and caspase-mediated apoptosis. Silvestrol represents a natural product scaffold that exhibits potent cytotoxic activity and could be used for the further study of autophagy and its relationship to apoptosis in cancer cells.

【 授权许可】

CC BY   
© Chen et al. 2016