کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5850078 | 1561773 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
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
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کلمات کلیدی
JnkDR5DR4ERKPARPc-Jun N-terminal kinase - C-Jun N-terminal kinasep38 MAPK - P38 MAPKROS - ROSIlimaquinone - الیماکوینونTUNEL - تونلCHOP - تکه کردنApoptosis - خزان یاختهایTRAIL - قطارtumor necrosis factor-related apoptosis-inducing ligand - لیگاند ناشی از آپوپتوز وابسته به عامل بیماری تومورCCAAT/enhancer-binding protein homologous protein - پروتئین هموسیستون پروتئین پروتئین CCAAT / پروتئین تقویت کنندهp38 mitogen-activated protein kinase - پروتئین کیناز متیوژن فعال p38extracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
دانش تغذیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Food and Chemical Toxicology - Volume 71, September 2014, Pages 51-59
Journal: Food and Chemical Toxicology - Volume 71, September 2014, Pages 51-59
نویسندگان
Minh Truong Do, MinKyun Na, Hyung Gyun Kim, Tilak Khanal, Jae Ho Choi, Sun Woo Jin, Seok Hoon Oh, In Hyun Hwang, Young Chul Chung, Hee Suk Kim, Tae Cheon Jeong, Hye Gwang Jeong,