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KMID : 1140120120170010027
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Cancer Prevention Research
2012 Volume.17 No. 1 p.27 ~ p.36
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Alliin Downregulates PMA-Induced Cyclooxygenase-2 Expression and Prostaglandin E2 Production through Sustained NF-κB Activation in Human Promonocytic U937 Cells
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Choi Yung-Hyun
Park Cheol
Choi Tae-Hyun
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Abstract
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Alliin (S-allyl-L-cysteine sulfoxide) is a sulfoxide that is a natural constituent of fresh garlic (Alliumsativum) and reported to possess many pharmacological activities including immune system enhancement, anti-diabetes, anti-hyperlipidemia, anti-oxidant, anti-cardiotoxicity, anti-angiogenesis and anti-cancer properties. However, the anti-inflammatory properties of alliin were unclear. In the present study, it was investigated the effects of alliin on the expression of cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE2) in phorbol 12-myristate-13-acetate (PMA)-stimulated human promonocytic U937 cells. In U937 cells stimulated with PMA to mimic inflammation, pre-treatment with alliin markedly inhibited expression of both COX-2 mRNA and protein, which was associated with attenuated the release of PGE2 in a dose-dependent manner. To investigate the mechanism by which alliin inhibits COX-2 gene expression and PGE2 production, we examined the effects of alliin on the PMA-induced activation of nuclear factor-kappaB (NF-κB) in U937 cells. Pre-treatment with alliin significantly attenuated the PMAinduced IkappaB (IκB) degradation and prevented the nuclear translocation of NF-κB. However, the elevated levels of early growth response gene-1 (Egr-1) expression by PMA were not reduced by the pre-treatment of alliin. These findings indicate that alliin derived from garlic exhibits anti-inflammatory properties by suppressing the transcription of COX-2 through the inactivation of NF-κB signaling pathway.
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KEYWORD
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Alliin, U937, COX-2, PGE2, NF-κB
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