1. Academic Validation
  2. Death receptor 5-mediated TNFR family signaling pathways modulate γ-humulene-induced apoptosis in human colorectal cancer HT29 cells

Death receptor 5-mediated TNFR family signaling pathways modulate γ-humulene-induced apoptosis in human colorectal cancer HT29 cells

  • Oncol Rep. 2011 Feb;25(2):419-24. doi: 10.3892/or.2010.1087.
Yu-Hsuan Lan 1 Yang-Chang Wu Kai-Wei Wu Jing-Gung Chung Chi-Cheng Lu Yuan-Liang Chen Tian-Shung Wu Jai-Sing Yang
Affiliations

Affiliation

  • 1 School of Pharmacy, Department of Pharmacology, China Medical University, Taichung 404, Taiwan, ROC.
Abstract

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.

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    Granzyme B/Caspase-8底物肽