期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 43, 期 4, 页码 568-580出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2007.05.009
关键词
curcumin; glutathione; tumor necrosis factor; nuclear factor-kappa B; reactive oxygen species; free radicals
资金
- NCI NIH HHS [CA91844, P01 CA091844-020004, P01 CA091844, P50CA97007, P01 CA124787, P50 CA097007, P01 CA124787-01A20002, P01 CA091844-010004] Funding Source: Medline
Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits antioxidant, anti-inflamminatory, and proapoptotic activities. We investigated whether the anti-inflaminatory and proapoptotic activities assigned to curcumin are mediated through its prooxidant/antioxidant mechanism. We found that TNF-mediated NF-kappa B activation was inhibited by curcumin; and glutathione reversed the inhibition. Similarly, suppression of TNF-induced AKT activation by curcumin was also abrogated by glutathione. The reducing agent also counteracted the inhibitory effects of curcumin on TNF-induced NF-kappa B-regulated antiapoptotic (Bcl-2, Bcl-xL, IAPI), proliferative (cyclin D1), and proinflaininatory (COX-2, NOS, and MMP-9) gene products. The suppression of TNF-induced AP-1 activation by curcumin was also reversed by glutathione. Also, the direct proapoptotic effects of curcumin were inhibited by glutathione and potentiated by depletion of intracellular glutathione by buthionine sulfoximine. Moreover, curcumin induced the production of reactive oxygen species and modulated intracellular GSH levels. Quenchers of hydroxyl radicals, however, were ineffective in inhibiting curcumin-mediated NF-kappa B suppression. Further, N-acetylcysteine partially reversed the effect of curcumin. Based on these results we conclude that curcumin mediates its apoptotic and anti-inflammatory activities through modulation of the redox status of the cell. (c) 2007 Elsevier Inc. All rights reserved.
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