TY - JOUR AB - A component from Emilia sonchifolia (L.) DC, γ-humulene, was investigated. Significantly decreased cell viability of human colorectal cancer HT29 cells in a dose-dependent manner with IC50 53.67±2.99 μM for 24-h treatment was found. γ-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 γ-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. γ-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-1ß-converting enzyme inhibitory protein (c-FLIP) by Western blot analysis. Consequently, γ-humulene-triggered cell death was significantly attenuated by DR5 siRNA and the caspase-8 inhibitor. Based on our results, we suggest that γ-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. AD - School of Pharmacy, China Medical University, Taichung 404, Taiwan, R.O.C. null School of Pharmacy, China Medical University, No 91, Hsueh-Shih Road, Taichung 40402, Taiwan, R.O.C. Department of Pharmacology, China Medical University, No 91, Hsueh-Shih Road, Taichung 40402, Taiwan. R.O.C. AU - Lan,Yu-Hsuan AU - Wu,Yang-Chang AU - Wu,Kai-Wei AU - Chung,Jing-Gung AU - Lu,Chi-Cheng AU - Chen,Yuan-Liang AU - Wu,Tian-Shung AU - Yang,Jai-Sing DA - 2011/02/01 DO - 10.3892/or.2010.1087 EP - 424 IS - 2 JO - Oncol Rep KW - γ-humulene herbal medicine TNFR family apoptotic signaling death receptor 5 human colorectal cancer HT29 cells PY - 2011 SN - 1021-335X 1791-2431 SP - 419 ST - Death receptor 5-mediated TNFR family signaling pathways modulate γ-humulene-induced apoptosis in human colorectal cancer HT29 cells T2 - Oncology Reports TI - Death receptor 5-mediated TNFR family signaling pathways modulate γ-humulene-induced apoptosis in human colorectal cancer HT29 cells UR - https://doi.org/10.3892/or.2010.1087 VL - 25 ER -