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Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1‐mediated nuclear factor‐κB pathway and subsequently downregulating expression of matrix metalloproteinases
Author(s) -
Liu PoLen,
Tsai JongRung,
Charles Albert Linton,
Hwang JhiJhu,
Chou ShahHwa,
Ping YuehHsin,
Lin FengYen,
Chen YuhLien,
Hung ChunYing,
Chen WenChi,
Chen YungHsiang,
Chong InnWen
Publication year - 2010
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200900550
Subject(s) - resveratrol , cancer research , matrix metalloproteinase , metastasis , heme oxygenase , a549 cell , adenocarcinoma , lung cancer , angiogenesis , chemistry , gene silencing , biology , heme , cancer , medicine , pathology , enzyme , biochemistry , gene
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 (∼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 μM) 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)‐κB inhibitor induced a marked reduction in MMP‐9 and MMP‐2 expression, suggesting NF‐κB 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‐κB pathway.