Ilimaquinone induces death receptor expression and sensitizes human colon cancer cells to TRAIL-induced apoptosis through activation of ROS-ERK/p38 MAPK-CHOP signaling pathways

Title
Ilimaquinone induces death receptor expression and sensitizes human colon cancer cells to TRAIL-induced apoptosis through activation of ROS-ERK/p38 MAPK-CHOP signaling pathways
Author(s)
정태천MT Do[MT Do]나민균[나민균]김형균[김형균]T Khanal[T Khanal]최재호[최재호]진순우[진순우]오석훈[오석훈]황인현[황인현]정영철[정영철]김희숙[김희숙]정혜광[정혜광]
Keywords
ENDOPLASMIC-RETICULUM STRESS; DOWN-REGULATION; SPONGE METABOLITE; LIGAND RESISTANCE; GOLGI MEMBRANES; CARCINOMA-CELLS; MELANOMA-CELLS; UP-REGULATION; C-FLIP; DR5
Issue Date
201409
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.71, pp.51 - 59
Abstract
TRAIL induces apoptosis in a variety of tumor cells. However, development of resistance to TRAIL is a major obstacle to more effective cancer treatment. Therefore, novel pharmacological agents that enhance sensitivity to TRAIL are necessary. In the present study, we investigated the molecular mechanisms by which ilimaquinone isolated from a sea sponge sensitizes human colon cancer cells to TRAIL. Ilimaquinone pretreatment significantly enhanced TRAIL-induced apoptosis in HCT 116 cells and sensitized colon cancer cells to TRAIL-induced apoptosis through increased caspase-8, -3 activation, PARP cleavage, and DNA damage. Ilimaquinone also reduced the cell survival proteins Bcl2 and Bcl-xL, while strongly up-regulating death receptor (DR) 4 and DR5 expression. Induction of DR4 and DR5 by ilimaquinone was mediated through up-regulation of CCAAT/enhancer-binding protein homologous protein (CHOP). The up-regulation of CHOP, DR4 and DR5 expression was mediated through activation of extracellular-signal regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Finally, the generation of ROS was required for CHOP and DR5 up-regulation by ilimaquinone. These results demonstrate that ilimaquinone enhanced the sensitivity of human colon cancer cells to TRAIL-induced apoptosis through ROS-ERK/p38 MAPK-CHOP-mediated up-regulation of DR4 and DR5 expression, suggesting that ilimaquinone could be developed into an adjuvant chemotherapeutic drug. (C) 2014 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/30842http://dx.doi.org/10.1016/j.fct.2014.06.001
ISSN
0278-6915
Appears in Collections:
약학대학 > 약학부 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE