|ISHS Acta Horticulturae 848: II International Humulus Symposium
LUPULONE, A HOP PHYTOCHEMICAL, ACTIVATES DIFFERENT APOPTOTIC PATHWAYS IN HUMAN COLON TUMOR CELLS AND IN THEIR DERIVED METASTATIC CELLS
|Authors: ||V. Lamy, F. GossÚ, F. Raul, M. Chaabi, A. Lobstein|
|Keywords: ||apoptosis, lupulone, DR4/DR5, TRAIL, caspases, mitochondria, colon cancer|
The objective of our study was to compare death signalling pathways triggered by lupulone, a beta-acid of hops, in TRAIL-sensitive human colon cancer cells (SW480) and in their derived TRAIL-resistant metastatic cells (SW620). We showed that lupulone (74 ÁM) up-regulated the expression of TRAIL DR4/DR5 death receptors at the cell surface of both cell lines.
In SW480 cells, lupulone triggered cell death through a cross-talk between TRAIL-DR4/DR5 and the mitochondrial (intrinsic) pathways involving caspase-8 activation and Bid protein cleavage.
As a consequence depolarization of the mitochondrial membrane occured and cytochrome c was released into the cytosol leading to the activation of caspases-9 and -3. In the metastatic SW620 cells, lupulone restored the sensitivity of these cells to TRAIL and activated the extrinsic apoptotic pathway via DR4/DR5 death receptors and the direct involvement of the caspase-8/caspase-3 cascade.
The demonstration that lupulone is able to activate TRAIL-death signalling pathways even in TRAIL resistant cancer cells (SW620) highlights the potential of this natural compound for cancer therapy.
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