Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor-kappa B and stimulatory protein-1

Huang, Chin-Shiu; Fan, Yang-En; Lin, Chia-Chen; Hu, Miao‐Lin

doi:10.1016/j.jnutbio.2006.08.007

Cited by 112 publications

(89 citation statements)

References 52 publications

(51 reference statements)

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“…For example, curcumin interferes with the activities of MMP-2 and MMP-9, reducing the degradation of extracellular matrix, which forms the basis of angiogenic switch (Chen et al, 2004). Moreover, lycopene decreases the secretion of MMP-9 via the NF-B signaling pathway, leading to the inhibition of SK-Hep-1 cell invasion (Huang et al, 2007). Vanillin, at noncytotoxic concentrations, has been shown to inhibit the invasion and migration of cancer cells in vitro and significantly reduces the numbers of lung-metastasized colonies in mice (Lirdprapamongkol et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Vanillin Inhibits Matrix Metalloproteinase-9 Expression through Down-Regulation of Nuclear Factor-κB Signaling Pathway in Human Hepatocellular Carcinoma Cells

Liang

et al. 2008

Mol Pharmacol

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Vanillin has been reported to exhibit anti-invasive and antimetastatic activities by suppressing the enzymatic activity of matrix metalloproteinase-9 (MMP-9). However, the underlying mechanism of anti-invasive activity remains unclear so far. Herein we demonstrate that vanillin reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 gelatinolytic activity and suppressed cell invasion through the down-regulation of MMP-9 gene transcription in HepG2 cells. Vanillin significantly reduced the 6.6-fold invasive capacity of HepG2 cells in noncytotoxic concentrations, and this anti-invasive effect was concentration-dependent in the Matrigel invasion assay. Moreover, vanillin significantly suppressed the TPA-induced enzymatic activity of MMP-9 and decreased the induced mRNA level of MMP-9. Analysis of the transcriptional regulation indicated that vanillin suppressed MMP-9 transcription by inhibiting nuclear factor-B (NF-B) activity. Western blot further confirmed that vanillin inhibited NF-B activity through the inhibition of IB-␣ phosphorylation and degradation. In conclusion, vanillin might be a potent antiinvasive agent that suppresses the MMP-9 enzymatic activity via NF-B signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Vanillin Inhibits Matrix Metalloproteinase-9 Expression through Down-Regulation of Nuclear Factor-κB Signaling Pathway in Human Hepatocellular Carcinoma Cells

Liang

et al. 2008

Mol Pharmacol

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“…Additional studies by Huang et al [122] demonstrated that lycopene strongly inhibited the invasion of SK-Hep-1 cells and this effect was mediated by inhibition of NF-κB and stimulatory protein-1 binding activity leading to a decrease in the secretion of MMP-9. Lycopene also decreased the level of ROS and insulinlike growth factor-1 (IGF-1R), albeit to a lesser extent [122] . Sesquiterpenes: α-Bisabolbol, a sesquiterpene, was found to induce cytotoxicity in HepG2 cells.…”

Section: Tetraterpenesmentioning

confidence: 92%

“…Antioxidant mechanisms 2.5-20 μmol/L Kozuki et al [114] Inhibited the migration of SK-Hep-1 cells 1-20 μmol/L Huang et al [115] Delayed the proliferation and improved the differentiation of oval cells obtained from neoplastic liver ↑albumin; ↑fibrinogen; ↑ hapatoglobin 5 μmol/L Wójcik et al [116] Exerted genotoxic and cytotoxic effects in HepG2 cells ↑apoptosis; ↑necrosis; ↑TBARS 4-8 μmol/L Yurtcu et al [117] Fucoxanthin Inhibited the growth of HepG2 cells ⊥G0/G1; ↓cyclin D1, D3; ↓cdk4; ↓pRb 10-50 μmol/L Das et al [118] Exhibited antiproliferative effect against SK-Hep-1 cells ↑apoptosis; ⊥G0-G1; ↑GJIC; ↑Cx43; ↑Cx32; ↓pJNK; ↓pERK; ↑[Ca] [119] Lycopene Suppressed the invasive property of AH109A cells [114] Induced an inhibitory effect on the growth of Hep3b cells [120] Displayed antimigration and anti-invasive activity in SK-Hep-1 cells [115] Inhibited adhesion, invasion and migration of SK-Hep-1 cells ↓MMP-9, -2 0.1-50 μmol/L Hwang et al [121] Inhibited SK-Hep-1 cell invasion ↓MMP-9; ↓NF-κB; ↑IκBα; ↓Sp1; ↓IGF-1R; ↓ROS 1-10 μmol/L Huang et al [122] Sesquiterpenes α-Bisabolbol Induced cytoxicity in HepG2 cells ↑apoptosis; ↑caspase-8, -9; ↑cyt. c; ↑Bax; ↑Bak; ↓Bcl-2; ↑p53; ↑NF-κB; ↑Fas [123] Dehydrocostuslactone…”

Section: Lupeolmentioning

confidence: 99%

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Thoppil

Bishayee²

2011

WJH

267

143

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Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called "isoprenoids") are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed.

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“…Hwang and Lee [44] showed that lycopene at 5 and 10 µM (higher than physiologically relevant concentrations) could decrease the gelatinolytic activities of the matrix metalloproteinases MMP-2 and MMP-9 and inhibit the adhesion, invasion and migration of SK-Hep1 cells. At similar lycopene concentrations, Huang et al confirmed that MMP-9 expression was suppressed in SK-Hep-1 cells [45] and found that the metastasis suppressor gene nm23-H1 was induced [46]. These studies indicate that lycopene, at least at high doses that might not be physiologically attainable, can inhibit metastasis and invasion by hepatocarcinoma cells.…”

Section: Cell Invasion and Metastasismentioning

confidence: 92%

Multitargeted therapy of cancer by lycopene

2008

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An acyclic, non-provitamin A carotene, lycopene is responsible for the red pigmentation of ripe tomatoes and some other edible fruits such as watermelon and papaya. Lycopene is also a potent antioxidant and scavenger of free radicals. Multiple retrospective and prospective epidemiological studies have indicated that the consumption of tomato products containing lycopene is associated with a reduced risk of prostate cancer. These epidemiological studies are supported by numerous in vitro assays using cell cultures that show anti-cancer activities and cancer chemoprevention activities of lycopene in many cell lines including prostate cancer cells. These activities include inducing apoptosis, inhibiting metastasis, preventing oxidative stress, and up-regulating the antioxidant response element so that cells can produce cytoprotective enzymes against prooxidants and electrophiles. In vivo animal studies and Phase I and II clinical trials have shown that lycopene supplements are non-toxic and that lycopene is orally bioavailable. Furthermore, lycopene is concentrated in prostate tissue and localized to the nucleus. In addition, some oxygenated metabolites of lycopene have been identified, and might be active as chemoprevention agents. The next phase of research concerning lycopene as a chemoprevention agent will be Phase II clinical trials of efficacy that are placebo-controlled, randomized and double blind. These clinical trials are required to establish the efficacy of lycopene supplementation.

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Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor-kappa B and stimulatory protein-1

Cited by 112 publications

References 52 publications

Vanillin Inhibits Matrix Metalloproteinase-9 Expression through Down-Regulation of Nuclear Factor-κB Signaling Pathway in Human Hepatocellular Carcinoma Cells

Vanillin Inhibits Matrix Metalloproteinase-9 Expression through Down-Regulation of Nuclear Factor-κB Signaling Pathway in Human Hepatocellular Carcinoma Cells

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Multitargeted therapy of cancer by lycopene

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