Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γ associated mechanisms

Chuang, Cheng‐Hung; Yeh, Chiao-Lin; Yeh, Shu-Lan; Lin, En‐Shyh; Wang, Li-Yu; Wang, Ying-Hsuna

doi:10.1016/j.jnutbio.2016.03.011

Cited by 61 publications

(38 citation statements)

References 42 publications

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“…PPAR-g is a nuclear receptor transcription factor which plays a key role in the regulation of adipocytes differentiation and adipokines production and secretion (e.g. APN) and is also involved in lung, pancreatic, thyroid or colorectal cancer development (Polvani et al, 2016,Tavares et al, 2016,Friedrich et al, 2016Chuang et al, 2016). Dietary FAs are able to regulate adipose tissue secretory function as well (Stryjecki and Mutch, 2011), altering the secretion of APN, leptin, TNF-a and IL-6 (Drevon, 2005;Stryjecki and Mutch, 2011).…”

Section: Adipokinesmentioning

confidence: 99%

Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis

Saavedra‐García

Nichols

Mahmud

et al. 2018

Molecular and Cellular Endocrinology

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Keywords:Fatty acids Cancer Lipid metabolism FOXO3 FOXM1 AKT/PI3K pathway a b s t r a c t Obesity and cachexia represent divergent states of nutritional and metabolic imbalance but both are intimately linked to cancer. There is an extensive overlap in their signalling pathways and molecular components involved such as fatty acids (FAs), which likely play a crucial role in cancer. Forkhead box (FOX) proteins are responsible of a wide range of transcriptional programmes during normal development, and the FOXO3-FOXM1 axis is associated with cancer initiation, progression and drug resistance.Free fatty acids (FFAs), FA synthesis and b-oxidation are associated with cancer development and progression. Meanwhile, insulin and some adipokines, that are up-regulated by FAs, are also involved in cancer development and poor prognosis. In this review, we discuss the role of FA metabolism in cancer and how FA metabolism integrates with the FOXO3-FOXM1 axis. These new insights may provide leads to better cancer diagnostics as well as strategies for tackling cancer development, progression and drug resistance.

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Section: Adipokinesmentioning

confidence: 99%

Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis

Saavedra‐García

Nichols

Mahmud

et al. 2018

Molecular and Cellular Endocrinology

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“…The gene encoding NM23-H1 is a suppressor of tumor metastasis; research has revealed that it may reduce MMP-2 and -9 expression in various types of cancer cells (18)(19)(20)(21)35,42,43). Boissan et al (19) previously reported that NM23-H1 silencing promotesthe extracellular matrix invasion of HepG2 cells by up regulating numerous MMPs, including MMP-2.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor cell migration was assayed in transwell chambers according to the methods reported by Repesh (34), with certain modifications as previously described by Chuang et al (35). Briefly, transwell chambers with 6.5-mm polycarbonate filters of 8-µm pore size were used.…”

Section: Chemicalsmentioning

confidence: 99%

“…Expression levels of NM23-H1, MMP-2, E-cadherin, β-catenin and, TIMP-2 proteins were determined by western blotting. Western blot analysis was performed as described previously (35). Briefly, the medium was removed and cells were lysed with protein lysis buffer (50 mM Tris-HCl buffer pH 7.4, 1 mM EDTA, 5% SDS, 1 mM phenylmethylsulfonyl fluoride, 1X protease inhibitor cocktail).…”

Section: Chemicalsmentioning

confidence: 99%

“…MMP-2 activity was assayed using gelatin zymography according to the method reported by Hwang et al (36), with certain modifications, as previously described in a study by Chuang et al (35). The cells (5x10 4 cells/ml) were pretreated with ILL or CUM in RPMI-1640 medium containing 10% FBS for 24 h. Following two washes with PBS, the cells were incubated in serum-free RPMI-1640 medium for 24 h. Subsequently, the culture medium was harvested and stored at -20˚C until use.…”

Section: Chemicalsmentioning

confidence: 99%

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Anti-metastatic effects of isolinderalactone via the inhibition of MMP-2 and up regulation of NM23-H1 expression in human lung cancer A549 cells

et al. 2018

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Abstract. Metastatic lung cancer is a leading cause of mortality and has a mortality rate of ≥90%. Isolinderalactone (ILL) is a sesquiterpene lactone compound that has been used in traditional Chinese medicine. Research has demonstrated that ILL has anti-inflammatory and anti-proliferative properties; however, to the best of our knowledge, studies investigating whether ILL can inhibit lung cancer cell metastasis have not been conducted. In the present study, 1-10 µM ILL was applied in the culturing of the A549 lung cancer cell line to investigate the effects of ILL on the invasion and migration of lung cancer cells, including whether the possible mechanisms of ILL are associated with the expression of matrix metalloproteinase (MMP)-2 and NME/NM23 nucleoside diphosphate kinase 1 (NM23-H1) genes. The results of the present study indicated that ILL inhibited the invasion and migration of the A549 cancer cells and exhibited a dose-response association. ILL also significantly inhibited the protein expression and activity of MMP-2 (P<0.05), exhibiting a trend similar to that of its invasion-and migration-associated properties. Further research revealed that ILL significantly increased the expression of NM23-H1 protein and inhibited the expression of β-catenin protein (P<0.05). The results of the present study is, to the best of our knowledge, the first to confirm that ILL can inhibit the invasion and migration of A549 cancer cells, with the possible mechanisms potentially involving the inhibition of MMP-2 and β-catenin protein expression resulting from the up regulation of NM23-H1 expression. IntroductionCancer is a leading cause of mortality; ~8.2 million people worldwide succumbed to cancer-associated mortality in 2012, with lung cancer accounting for ~1.59 million cases of mortality, or ~20% of the total (1). Lung cancer cell metastasis is a primary cause of mortality and those that experience it have a mortality rate of ≥90% (2). When it metastasizes, lung cancer has a 95% chance of affecting local lymph nodes and an 80% chance of affecting other organs (3,4). Thus, in clinical terms, the overall 5-year survival rate from the time of diagnosis to mortality for patients with lung cancer undergoing treatment is only 10-15% (5). Cancer cell metastasis is a complex multistep process involving invasion and migration (6-8). Matrix metalloproteinases (MMPs) are zinc/calcium-dependent endopeptidases involved in the degradation of the extracellular matrix, two examples of which are MMP-2 and -9 (7,9). MMP-2 is a notable factor in the development of tumor metastasis (7,10). MMP-2 is highly expressed in malignant tumors and serves a key role in cancer invasion and angiogenesis (7,11). The inhibition of MMP-2 is, therefore, an effective strategy for preventing tumor cell metastasis (11,12). The NME/NM23 nucleoside diphosphate kinase 1 (NM23) gene was first identified in the murine melanoma cell line exhibiting high metastatic activity; increasing the expression of this gene may also reduce the metastatic activity of tumor cel...

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Design, Synthesis, and Biological Evaluation of Novel Quercetin Derivatives as PPAR‐γ Partial Agonists by Modulating Epithelial–Mesenchymal Transition in Lung Cancer Metastasis

et al. 2023

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Epithelial‐to‐mesenchymal transition (EMT) is responsible for driving metastasis of multiple cancer types including lung cancer. Peroxisome proliferator‐activated receptor (PPAR)‐γ, a ligand‐activated transcription factor, controls expression of variety of genes involved in EMT. Although several synthetic compounds act as potent full agonists for PPAR‐γ, their long term application is restricted due to serious adverse effects. Therefore, partial agonists involving reduced and balanced PPAR‐γ activity are more effective and valued. A previous study discerned the efficacy of quercetin and its derivatives to attain favorable stabilization with PPAR‐γ. Here this work is extended by synthesizing five novel quercetin derivatives (QDs) namely thiosemicarbazone (QUETSC)) and hydrazones (quercetin isonicotinic acid hydrazone (QUEINH), quercetin nicotinic acid hydrazone (QUENH), quercetin 2‐furoic hydrazone (QUE2FH), and quercetin salicyl hydrazone (QUESH)) and their effects are analyzed in modulating EMT in lung cancer cell lines via PPAR‐γ partial activation. QDs‐treated A549 cells diminish cell proliferation strongly at nanomolar concentration compared to NCI‐H460 cells. Of the five screened derivatives, QUETSC, QUE2FH, and QUESH exhibit the property of partial activation as compared to the overexpressive level of rosiglitazone. Consistently, these QDs also suppress EMT process by markedly downregulating the levels of mesenchymal markers (Snail, Slug, and zinc finger E‐box binding homeobox 1) and concomitant upregulation of epithelial marker (E‐cadherin).

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Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γ associated mechanisms

Cited by 61 publications

References 42 publications

Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis

Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis

Anti-metastatic effects of isolinderalactone via the inhibition of MMP-2 and up regulation of NM23-H1 expression in human lung cancer A549 cells

Design, Synthesis, and Biological Evaluation of Novel Quercetin Derivatives as PPAR‐γ Partial Agonists by Modulating Epithelial–Mesenchymal Transition in Lung Cancer Metastasis

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