Rotundarpene prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8-and Bid-pathways and the mitochondrial pathway

被引:14
作者
Lee, Da Hee [1 ,2 ]
Nam, Yoon Jeong [1 ,2 ]
Kim, Yun Jeong [1 ,2 ]
Lee, Min Won [3 ]
Lee, Chung Soo [1 ,2 ]
机构
[1] Chung Ang Univ, Dept Pharmacol, Coll Med, Seoul 156756, South Korea
[2] Chung Ang Univ, Skin Barrier Network Human Resources Dev Team BK2, Seoul 156756, South Korea
[3] Chung Ang Univ, Coll Pharm, Pharmacognosy Lab, Seoul 156756, South Korea
基金
新加坡国家研究基金会;
关键词
TRAIL; Rotundarpene; Human keratinocytes; Apoptosis-related protein activation; Skin diseases; INFLAMMATORY MEDIATORS; CELL-DEATH; PERMEABILITY TRANSITION; STIMULATED PRODUCTION; NITRIC-OXIDE; CANCER CELLS; ACID; PATHOGENESIS; INVOLVEMENT; ACTIVATION;
D O I
10.1007/s00210-014-1051-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The extract and hemiterpene glycosides of Ilex rotunda Thunb have demonstrated antioxidant and anti-inflammatory effects. Nevertheless, the effect of rotundarpene on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be involved in skin diseases has not been studied. In this respect, we investigated the effect of rotundarpene on TRAIL-induced apoptosis in human keratinocytes. TRAIL triggers apoptosis by inducing a decrease in the cytosolic levels of Bid, Bcl-2, Bcl-xL, and survivin proteins, increase in the cytosolic levels of Bax, and increase in the mitochondrial levels of VDAC1, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases (-8, -9, and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. Treatment with rotundarpene prevented TRAIL-induced changes in the levels of apoptosis-related proteins, formations of reactive oxygen species and nitric oxide, nuclear damage, and cell death. These results suggest that rotundarpene may reduce TRAIL-induced apoptosis in human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated cell death pathway, which is associated with the formation of reactive oxygen species and reactive nitrogen species. These data suggest that rotundarpene appears to be effective in the prevention of TRAIL-induced apoptosis-mediated skin diseases.
引用
收藏
页码:1209 / 1219
页数:11
相关论文
共 43 条
[21]   Rotundarpene inhibits Toll-like receptor 2 activation-induced production of inflammatory mediators in keratinocytes by suppressing the Akt and NF-κB pathways [J].
Kim, Yun Jeong ;
Jung, Eun Byul ;
Lee, Min Sung ;
Seo, Seong Jun ;
Kim, Manh Heun ;
Lee, Min Won ;
Lee, Chung Soo .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2014, 18 (02) :325-332
[22]   Following a TRAIL: Update on a ligand and its five receptors [J].
Kimberley, FC ;
Screaton, GR .
CELL RESEARCH, 2004, 14 (05) :359-372
[23]   3,4,5-Tricaffeoylquinic acid inhibits tumor necrosis factor-α-stimulated production of inflammatory mediators in keratinocytes via suppression of Akt- and NF-κB-pathways [J].
Lee, Chung Soo ;
Lee, Seon Ae ;
Kim, Yun Jeong ;
Seo, Seong Jun ;
Lee, Min Won .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2011, 11 (11) :1715-1723
[24]   3,4,5-Tricaffeoylquinic Acid Inhibits the Lipopolysaccharide-Stimulated Production of Inflammatory Mediators in Keratinocytes [J].
Lee, Seon Ae ;
Jung, Eun Byul ;
Lee, Seon Hwa ;
Kim, Yun Jeong ;
Bang, Hyoweon ;
Seo, Seong Jun ;
Choi, Young Wook ;
Kim, Manh Heun ;
Lee, Min Won ;
Lee, Chung Soo .
PHARMACOLOGY, 2012, 90 (3-4) :183-192
[25]  
Li ChaoSheng Li ChaoSheng, 2012, Journal of Medicinal Plants Research, V6, P2224
[26]   Death receptors: Targets for cancer therapy [J].
Mahmood, Zafar ;
Shukla, Yogeshwer .
EXPERIMENTAL CELL RESEARCH, 2010, 316 (06) :887-899
[27]   Mitochondria and apoptosis [J].
Mignotte, B ;
Vayssiere, JL .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1998, 252 (01) :1-15
[29]   Nitric oxide and peroxynitrite in health and disease [J].
Pacher, Pal ;
Beckman, Joseph S. ;
Liaudet, Lucas .
PHYSIOLOGICAL REVIEWS, 2007, 87 (01) :315-424
[30]   The Anti-oxidative and Anti-inflammatory Effects of Caffeoyl Derivatives from the Roots of Aconitum koreanum R. RAYMOND [J].
Park, Kwan Hee ;
Park, Min ;
Choi, Sun Eun ;
Jeong, Mi Sook ;
Kwon, Joo Hee ;
Oh, Myung Hwan ;
Choi, Hyung Kyun ;
Seo, Seong Jun ;
Lee, Min Won .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2009, 32 (12) :2029-2033