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-1β- converting enzyme inhibitory protein (c-FLIP) by Western blot analysis. Consequently, α-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.
CITATION STYLE
Lan, Y. U. H., Wu, Y. C., Wu, K. W., Chung, J. G., Lu, C. C., Chen, Y. L., … Yang, J. S. (2011). Death receptor 5-mediated TNFR family signaling pathways modulate γ-humulene-induced apoptosis in human colorectal cancer HT29 cells. Oncology Reports, 25(2), 419–424. https://doi.org/10.3892/or.2010.1087
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