Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases
Journal
Molecular Nutrition and Food Research
Journal Volume
54
Journal Issue
SUPPL. 2
Pages
S196-S204
Date Issued
2010
Author(s)
Liu P.-L.
Tsai J.-R.
Charles A.L.
Hwang J.-J.
Chou S.-H.
Ping Y.-H.
Lin F.-Y.
Hung C.-Y.
Chen W.-C.
Chen Y.-H.
Chong I.-W.
Abstract
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 (50μM) for 24h, 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. Copyright ? 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
SDGs
Other Subjects
antineoplastic agent; gelatinase A; gelatinase B; heme oxygenase 1; HMOX1 protein, human; immunoglobulin enhancer binding protein; matrix metalloproteinase; MMP2 protein, human; resveratrol; small interfering RNA; stilbene derivative; adenocarcinoma; article; cancer invasion; cell motion; cell survival; down regulation; drug antagonism; drug effect; gene silencing; genetics; human; lung non small cell cancer; lung tumor; metabolism; metastasis; osmolarity; pathology; signal transduction; tumor cell line; Adenocarcinoma; Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cell Survival; Down-Regulation; Gene Silencing; Heme Oxygenase-1; Humans; Lung Neoplasms; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Neoplasm Invasiveness; NF-kappa B; Osmolar Concentration; RNA, Small Interfering; Signal Transduction; Stilbenes
Type
journal article