請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/70863
標題: Death receptor 5-mediated TNFR family signaling pathways modulate gamma-humulene-induced apoptosis in human colorectal cancer HT29 cells
作者: Lan, Y.H.
Wu, Y.C.
Wu, K.W.
Chung, J.G.
Lu, C.C.
Chen, Y.L.
Wu, T.S.
Yang, J.S.
關鍵字: gamma-humulene
herbal medicine
TNFR family apoptotic signaling
death
receptor 5
human colorectal cancer HT29 cells
trail-induced apoptosis
colon-cancer
emilia-sonchifolia
independent
pathways
mitotic arrest
induction
activation
期刊/報告no:: Oncology Reports, Volume 25, Issue 2, Page(s) 419-424.
摘要: A component from Emilia sonchifolia (L.) DC, gamma-humulene, was investigated. Significantly decreased cell viability of human colorectal cancer HT29 cells in a dose-dependent manner with IC(50) 53.67 +/- 2.99 mu M for 24-h treatment was found. gamma-Humulene induced apoptotic cell death and apoptosis was confirmed by morphological assessment. The staining with propidium iodide (PI) and flow cytometric analysis also showed that gamma-humulene significantly promoted the sub-G1 phase (an apoptotic population) in HT29 cells. Colorimetric assays indicated that pretreatment with a specific inhibitor of caspase-8 (Z-IETD-FMK) significantly reduced activities of caspase-8 and caspase-3 in examined HT29 cells. gamma-Humulene stimulated the death receptor 5 (DR5), DR4, Fas-associated protein with death domain (FADD), the cleavage of caspase-8 and cleavage caspase-3, but reduced the protein levels of cellular Fas-associated death-domain-like IL-1 beta-converting enzyme inhibitory protein (c-FLIP) by Western blot analysis. Consequently, gamma-humulene-triggered cell death was significantly attenuated by DR5 siRNA and the caspase-8 inhibitor. Based on our results, we suggest that gamma-humulene induced apoptotic cell death in HT29 cells through a DR5-mediated caspase-8 and -3-dependent signaling pathway. Therefore, this agent might be useful for developing new therapeutic regimens for treatment of colorectal cancer in the future.
URI: http://hdl.handle.net/11455/70863
ISSN: 1021-335X
文章連結: http://dx.doi.org/10.3892/or.2010.1087
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