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Issue 1095 coverSignal Transduction Pathways, Part C: Cell Signaling in Health and Disease Volume 1095 published December 2006
Ann. N.Y. Acad. Sci. 1095: 564–573 (2007). doi: 10.1196/annals.1397.061
Copyright © 2007 by the New York Academy of Sciences
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Part III. Chemoprevention

Possible Link Between NO Concentrations and COX-2 Expression in Systems Treated with Soy-Isoflavones

JANG-IN SHINa, YUN-KYUNG LEEa, YOUNG MIN KIMb, JIN-TAEK HWANGc AND OCK JIN PARKa

a Department of Food and Nutrition, Hannam University, Daejeon 306-791, Korea b Department of Biological Sciences, Hannam University, Daejeon 306-791, Korea c Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, Kyung Hee University College of Medicine, Seoul 130-701, Korea

Key Words: nitric oxide • COX-2 • soy-isoflavones (genistein) • in vivo system • mammalian cancer cells • SNP • AMPK

Address for correspondence: Ock Jin Park, Department of Food and Nutrition, Hannam University, Daejeon 306-791, Korea. Voice: +82-42-629-7493; fax: +82-42-629-7490.  e-mail: ojpark{at}hannam.ac.kr

The production of nitric oxide (NO) emerges as an essential determinant in auto- and paracrine signaling. NO is known to be generated under inflammatory conditions, carcinogenesis, and circulatory shock. The large amount of NO produced in response to cytokines plays an important role in inflammatory conditions. Cyclooxygenase (COX), the central enzyme in prostanoid biosynthesis, is involved in the first step of prostanoid synthesis from arachidonic acid. The reported studies to evaluate the relationship between NO and COX-2 have revealed both inhibitory and stimulatory effects of NO on COX-2 expression. Genistein, one of soy-isoflavones, is a polyphenolic flavonoid and a potent antioxidant and anti-inflammatory agent. In the present article, the effect of soy-isoflavones on NO production and COX-2 gene expression was examined. NO production by soy-isoflavones was greatly increased even though eNOS and iNOS expression were not different from nontreated control. The increment of NO was accompanied with the elevated expression of COX-2 and the concentrations of PGE2. The COX-2 stimulatory effect of soy-isoflavones appeared to be modulated by ERK-1 and -2 and p38. In mammalian cancer system, incubation with the NO donor sodium nitroprusside (SNP) resulted in a slight upregulation of COX-2, and cotreatment with genistein decreased COX-2 expression possibly by the activation of AMP-activated protein kinase (AMPK).






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