β-Caryophyllene oxide potentiates TNFα-induced apoptosis and inhibits invasion through down-modulation of NF-κB-regulated gene products

被引:66
作者
Kim, Chulwon [1 ]
Cho, Somi K. [2 ,3 ]
Kim, Ki-Dong [1 ]
Nam, Dongwoo [1 ]
Chung, Won-Seok [1 ]
Jang, Hyeung-Jin [1 ]
Lee, Seok-Geun [1 ]
Shim, Bum Sang [1 ]
Sethi, Gautam [4 ,5 ]
Ahn, Kwang Seok [6 ]
机构
[1] Kyung Hee Univ, Coll Korean Med, Seoul 130701, South Korea
[2] Jeju Natl Univ, Coll Appl Life Sci, Fac Biotechnol, Cheju 690756, South Korea
[3] Jeju Natl Univ, Subtrop Hort Res Inst, Cheju 690756, South Korea
[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117597, Singapore
[5] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117597, Singapore
[6] Kyung Hee Univ, Coll Korean Med, Dept Korean Pathol, Seoul 130701, South Korea
关键词
beta-Caryophyllene oxide; NF-kappa B; TNF alpha; Apoptosis; TUMOR-NECROSIS-FACTOR; ESSENTIAL OIL; CONSTITUTIVE ACTIVATION; CINNAMOMUM-OSMOPHLOEUM; TRANSCRIPTION FACTOR; CANCER CELLS; INDUCTION; SUPPRESSION; PATHWAYS; PROTEIN;
D O I
10.1007/s10495-013-0957-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
We have recently reported that beta-caryophyllene oxide (CPO) can induce apoptosis, suppress tumor growth, and inhibit metastasis through the suppression of signal transducer and activator of transcription 3, PI3K/AKT/mTOR/S6K1 signaling cascades and ROS-mediated MAPKs activation. In the present study, we found that CPO potentiated the apoptosis induced by tumor necrosis factor alpha (TNF alpha) and chemotherapeutic agents, suppressed TNF alpha-induced tumor cell invasion, all of which are known to require NF-kappa B activation. We found that TNF alpha stimulated the expression of gene products involved in anti-apoptosis (IAP1, IAP2, Bcl-2, Bcl-xL, and survivin), proliferation (COX-2, cyclin D1, and c-Myc), invasion (MMP 9 and ICAM-1), and angiogenesis (VEGF) and that CPO treatment suppressed their expression. Because these gene products are also regulated by proinflammatory transcription factor NF-kappa B, we postulated that CPO may mediate its effects by modulating the NF-kappa B pathway. We found that CPO blocked both inducible and constitutive NF-kappa B activation in a wide variety of tumor cells. CPO was also found to inhibit the TNF alpha-induced degradation of I kappa B alpha through the inhibition of activation of I kappa B alpha kinase and p65 nuclear translocation and phosphorylation. Interestingly, CPO failed to potentiate the apoptotic effect induced by TNF alpha in p65 (-/-) cells as compared to the wild-type. Thus, overall, our results indicate that the inhibition of NF-kappa B is one of major mechanisms by which CPO enhances TNF alpha-induced apoptosis and suppresses invasion.
引用
收藏
页码:708 / 718
页数:11
相关论文
共 31 条
[1]
Aggarwal BB, 2005, CANC TREAT, V126, P103, DOI 10.1007/0-387-24361-5_5
[2]
Signalling pathways of the TNF superfamily: A double-edged sword [J].
Aggarwal, BB .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (09) :745-756
[3]
Nuclear factor-κ-B:: The enemy within [J].
Aggarwal, BB .
CANCER CELL, 2004, 6 (03) :203-208
[4]
γ-tocotrienol inhibits nuclear factor-κB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and Potentiation of apoptosis [J].
Ahn, Kwang Seok ;
Sethi, Gautam ;
Krishnan, Koyamangalath ;
Aggarwal, Bharat B. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (01) :809-820
[5]
CYCLIN D1 IS A NUCLEAR-PROTEIN REQUIRED FOR CELL-CYCLE PROGRESSION IN G(1) [J].
BALDIN, V ;
LUKAS, J ;
MARCOTE, MJ ;
PAGANO, M ;
DRAETTA, G .
GENES & DEVELOPMENT, 1993, 7 (05) :812-821
[6]
Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-κB and IκBα kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis [J].
Bharti, AC ;
Donato, N ;
Singh, S ;
Aggarwal, BB .
BLOOD, 2003, 101 (03) :1053-1062
[7]
Bonizzi G, 1997, J IMMUNOL, V159, P5264
[8]
Study on the antiinflammatory activity of essential oil from leaves of Cinnamomum osmophloeum [J].
Chao, LK ;
Hua, KF ;
Hsu, HY ;
Cheng, SS ;
Liu, JY ;
Chang, ST .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2005, 53 (18) :7274-7278
[9]
Protein kinase C-ζ regulates transcription of the matrix metalloproteinase-9 gene induced by IL-1 and TNF-α in glioma cells via NF-κB [J].
Estève, PO ;
Chicoine, É ;
Robledo, O ;
Aoudjit, F ;
Descoteaux, A ;
Potworowski, EF ;
St-Pierre, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (38) :35150-35155
[10]
Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer [J].
Ferrara, N ;
Hillan, KJ ;
Gerber, HP ;
Novotny, W .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (05) :391-400