Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 54, Issue -, Pages S196-S204Publisher
WILEY-BLACKWELL
DOI: 10.1002/mnfr.200900550
Keywords
Heme oxygenase 1; Matrix metalloproteinase; Metastasis; Non-small cell lung cancer; Resveratrol
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Funding
- National Science Council [NSC 96-2314-B-037-064, NSC 97-2320-B-037-022-MY3, NSC 97-2320-B-039-022-MY3]
- Kaohsiung Medical University [Q096025, Q097044]
- China Medical University, Taiwan [CMU98-CT-10]
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Resveratrol exhibits potential anti-carcinogenic activities. Heme oxygenase-1 (HO-1) is involved in angiogenesis and tumor metastasis. Matrix metalloproteinases (MMPs) are key enzymes in the degradation of extracellular matrix, and their expression may be dysregulated in lung cancer metastasis. In this study, we investigated the anti-invasive mechanism of resveratrol in lung cancer cells. HO-1 was shown to be elevated (similar to 4.7-fold) in lung cancer tumor samples as compared with matched normal tissues. After treatment of lung adenocarcinoma cell line A549 cells with resveratrol (50 mu M) for 24 h, the migratory and invasive abilities (38 and 30% inhibition, respectively) of A549 cells were significantly reduced. Resveratrol significantly inhibited HO-1-mediated MMP-9 (35% inhibition) and MMP-2 (28% inhibition) expression in lung cancer cells. Nuclear factor (NF)-kappa B inhibitor induced a marked reduction in MMP-9 and MMP-2 expression, suggesting NF-kappa B pathway could play an important role. Furthermore, HO-1 inhibition and silencing significantly suppressed MMPs and invasion of lung cancer cells. Our results suggest that resveratrol inhibited HO-1 and subsequently MMP-9 and MMP-2 expression in lung cancer cells. The inhibitory effects of resveratrol on MMP expression and invasion of lung cancer cells are, in part, associated with the HO-1-mediated NF-kappa B pathway.
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