Carcinogenesis Advance Access published online on August 31, 2006
Carcinogenesis, doi:10.1093/carcin/bgl151
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea
* To whom correspondence should be addressed. Conjugated linoleic acid (CLA) has been reported to inhibit mouse skin carcinogenesis, particularly in the promotion stage, but underlying molecular mechanisms remain poorly understood. Since persistent induction of cyclooxygenase-2 (COX-2) is frequently implicated in carcinogenesis, we investigated the effect of cis-9,trans-11-CLA (9Z,11E-CLA) on the tumor promoter-induced COX-2 expression in HR-1 hairless mouse skin in vivo. Topical application of 9Z,11E-CLA caused significant inhibition of COX-2 expression at 6 h induced by 10 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) in HR-1 mouse skin. Since NF-
Received February 21, 2006
Revised August 2, 2006
Accepted August 16, 2006
CANCER PREVENTION
cis-9,trans-11-Conjugated linoleic acid down-regulates phorbol ester-induced NF-
Dal-Mi Hwang 1, Joydeb Kumar Kundu 1, Jun-Wan Shin 1, Hyong Joo Lee 2, and Young-Joon Surh 1 *
B activation and subsequent COX-2 expression in hairless mouse skin by targeting IB kinase and PI3K-Akt
2 Department of Food Science and Technology, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-742, South Korea
Young-Joon Surh, E-mail: surh{at}plaza.snu.ac.kr
Abstract 
B is known to regulate COX-2 gene expression, we determined the effect of 9Z,11E-CLA on TPA-induced NF-B activation. Treatment of mouse skin with 9Z,11E-CLA reduced TPA-induced DNA binding as well as nuclear translocation of NF-B by blocking phosphorylation and subsequent degradation of IB
. In addition, 9Z,11E-CLA attenuated TPA-induced phosphorylation of extracellular signal regulated protein kinase, p38 mitogen-activated protein kinase and Akt. To further elucidate the molecular mechanism underlying the inactivation of NF-B by 9Z,11E-CLA, we further investigated its effect on TPA-induced activation of IB kinase (IKK), an upstream kinase that regulates NF-B via phosphorylation and degradation of IB. 9Z,11E-CLA treatment down-regulated phosphorylation and catalytic activities of IKK/
in TPA-treated mouse skin. Co-treatment of mouse skin with the IKK-specific inhibitor SC-514 (1 µmol) attenuated TPA-induced activation of Akt and NF-B, and also the expression of COX-2 in hairless mouse skin. Taken together, 9Z,11E-CLA inhibits NF-B driven-COX-2 expression by blocking the IKK and PI3K-Akt signaling in TPA-treated hairless mouse skin in vivo, which may account for its previously reported anti-tumor promoting effects.B; IB kinase.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. E. Larsen, D. Cameron-Smith, and T. C. Crowe Conjugated Linoleic Acid Suppresses Myogenic Gene Expression in a Model of Human Muscle Cell Inflammation J. Nutr., January 1, 2008; 138(1): 12 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Kelley, N. E. Hubbard, and K. L. Erickson Conjugated Linoleic Acid Isomers and Cancer J. Nutr., December 1, 2007; 137(12): 2599 - 2607. [Abstract] [Full Text] [PDF]
|
|