Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells

被引:121
作者
Nonn, Larisa [1 ]
Duong, David [1 ]
Peehl, Donna M. [1 ]
机构
[1] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA
关键词
D O I
10.1093/carcin/bgl241
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
As inflammation emerges as a risk factor for prostate cancer (PCa), there is potential for chemoprevention by anti-inflaimmatory agents. Dietary phytochemicals have been shown to have chemopreventive properties which may include anti-inflammatory activities. In this study, we demonstrate a role for mitogen-activated protein kinase phosphatase-5 (MKP5) in mediating anti-inflammatory activities of the phytochemicals curcumin, resveratrol and [6]-gingerol. We utilized the cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta to increase p38-dependent nuclear factor kappa-B (NF kappa B) activation and expression of pro-inflammatory genes cyclooxygenase-2 (COX-2), IL-6 and IL-8 in normal prostatic epithelial cells. MKP5 over-expression decreased cytokine-induced NF kappa B activation, COX-2, IL-6 and IL-8 in normal prostatic epithelial cells, suggesting potent anti-inflammatory activity of MKP5. Pretreatment of cells with a p38 inhibitor mimicked the results observed with MKP5 over-expression, further implicating p38 inhibition as the main activity of MKP5. Curcumin, the phytochemical found in turmeric, up-regulated MKP5, subsequently decreasing cytokine-induced p38-dependent proinflammatory changes in normal prostatic epithelial cells. Resveratrol and [6]-gingerol, phytochemicals present in red wine and ginger, respectively, also up-regulated MKP5 in normal prostate epithelial cells. Moreover, we found that PCa cell lines DU 145, PC-3, LNCaP and LAPC-4 retained the ability to up-regulate MKP5 following curcumin, resveratrol and [6]-gingerol exposure, suggesting utility of these phytochemicals in PCa treatment. In summary, our findings show direct anti-inflammatory activity of MKP5 in prostate cells and suggest that up-regulation of MKP5 by phytochemicals may contribute to their chemopreventive actions by decreasing prostatic inflammation.
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收藏
页码:1188 / 1196
页数:9
相关论文
共 46 条
[1]  
[Anonymous], 2005, PROSTATE, DOI DOI 10.1002/pros.20212
[2]   Interleukin-1 - a major pleiotropic cyrtokine in tumor-host interactions [J].
Apte, RN ;
Voronov, E .
SEMINARS IN CANCER BIOLOGY, 2002, 12 (04) :277-290
[3]   1α, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis [J].
Bao, Bo-Ying ;
Yao, Jorge ;
Lee, Yi-Fen .
CARCINOGENESIS, 2006, 27 (09) :1883-1893
[4]   Engagement of tumor necrosis factor (TNF) receptor 1 leads to ATF-2-and p38 mitogen-activated protein kinase-dependent TNF-α gene expression [J].
Brinkman, BMN ;
Telliez, JB ;
Schievella, AR ;
Lin, LL ;
Goldfeld, AE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (43) :30882-30886
[5]   Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential upstream targets [J].
Cho, JW ;
Park, K ;
Kweon, GR ;
Jang, BC ;
Baek, WK ;
Suh, MH ;
Kim, CW ;
Lee, KS ;
Suh, SI .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2005, 37 (03) :186-192
[6]   Cyclooxygenase-2 (cox-2) expression is an independent predictor of prostate cancer recurrence [J].
Cohen, Brian L. ;
Gomez, Pablo ;
Omori, Yohei ;
Duncan, Robert C. ;
Civantos, Francisco ;
Soloway, Mark S. ;
Lokeshwar, Vinata B. ;
Lokeshwar, Bal L. .
INTERNATIONAL JOURNAL OF CANCER, 2006, 119 (05) :1082-1087
[7]   Interleukin-6: minor player or starring role in the development of hormone-refractory prostate cancer? [J].
Corcoran, NM ;
Costello, AJ .
BJU INTERNATIONAL, 2003, 91 (06) :545-553
[8]   Inflammation and cancer [J].
Coussens, LM ;
Werb, Z .
NATURE, 2002, 420 (6917) :860-867
[9]   p38 MAPK and NF-κB collaborate to induce interleukin-6 gene expression and release -: Evidence for a cytoprotective autocrine signaling pathway in a cardiac myocyte model system [J].
Craig, R ;
Larkin, A ;
Mingo, AM ;
Thuerauf, DJ ;
Andrews, C ;
McDonough, PM ;
Glembotski, CC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (31) :23814-23824
[10]   Sexual behaviour, history of sexually transmitted diseases, and the risk of prostate cancer:: a case-control study in Cuba [J].
Fernández, L ;
Galán, Y ;
Jiménez, R ;
Gutiérrez, A ;
Guerra, M ;
Pereda, C ;
Alonso, C ;
Riboli, E ;
Agudo, A ;
González, C .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2005, 34 (01) :193-197