Role of NAD(P)H:quinone oxidoreductase 1 on tumor necrosis factor-α-induced migration of human vascular smooth muscle cells

Lee, Syng‐Ook; Chang, Young‐Chae; Whang, Key; Kim, Cheorl-Ho; Lee, In-Seon

doi:10.1016/j.cardiores.2007.06.030

Cited by 23 publications

(22 citation statements)

References 25 publications

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“…The ability of NQO1 to drive human aortic vascular smooth muscle cell migration and invasion was previously demonstrated (35). Treatment with dicoumarol or transfection with NQO1 siRNA suppressed tumor necrosis factor α-induced cell migration by inhibiting MMP9 protein and mRNA expression (35,36). In the present study, NQO1 siRNA significantly decreased the migratory ability of CCA cells, which suggested a role for NQO1 in promoting the metastasis of CCA.…”

Section: Discussionsupporting

confidence: 56%

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Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells

et al. 2017

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Abstract. We previously reported that upregulation of NAD(P)H:quinone oxidoreductase 1 (NQO1) in cholangiocarcinoma (CCA; a fatal bile duct cancer) was associated with poor prognosis. It was also demonstrated that the suppression of NQO1 was able to enhance the chemosensitivity of CCA cells. In the present study, in order to elucidate the biological role of NQO1 in CCA, the effects of small interfering RNA (siRNA)-mediated knockdown of NQO1 on cell proliferation, cell cycle and migration were determined in KKU-100 CCA cells, which notably expressed NQO1. The cell proliferation ability and cell cycle distribution were identified by clonogenic cell survival assay and flow cytometric analysis, respectively. Wound healing and Transwell migration assays were performed to evaluate cell migration. The molecules involved in cell proliferation and migration were determined by western blot analysis and reverse transcription-quantitative polymerase chain reaction analysis. The results demonstrated that NQO1 siRNA-mediated knockdown effectively impaired colony formation capacity, induced cell cycle arrest at the G 1 phase and suppressed migration of KKU-100 cells. CCA cells transfected with NQO1 siRNA exhibited increased expression levels of p21 and decreased cyclin D1 protein expression levels. Furthermore, the ratio of matrix metalloproteinase 9/tissue inhibitors of metalloproteinases 1 (TIMP1) mRNA expression level was decreased in the NQO1-knockdown cells. Therefore, the present study provided evidence supporting the biological role of NQO1 in the regulation of cell proliferation, cell cycle and migration of CCA cells. Therefore, NQO1 may prove to be a potential molecular target to enhance CCA treatment.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells

et al. 2017

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“…These observations suggest that upregulation of NQO1 may be an adaptive mechanism to protect against oxidative and inflammatory stress. Indeed, it was shown that overexpression of NQO1 in cultured vascular endothelial and smooth muscle cells protected them not only from oxidative cytotoxicity, but also from cytokine-induced proinflammatory responses [22,23]. A recent study reported that activation of NQO1 prevented arterial restenosis by suppressing vascular smooth muscle cell proliferation in an animal model of balloon injury of carotid artery [24].…”

Section: Role Of Nqo1 In Atherogenesis In Experimental Modelsmentioning

confidence: 97%

NAD(P)H:Quinone Oxidoreductase 1 and its Potential Protective Role in Cardiovascular Diseases and Related Conditions

Zhu

2011

Cardiovasc Toxicol

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NAD(P)H: quinone oxidoreductase (NQO) represents a family of flavoproteins that catalyze the two-electron reduction of quinones and their derivatives. In mammalian systems, there are two members of NQO, namely, NQO1 and NQO2. NQO1 utilizes NAD(P)H, whereas NQO2 employs dihydronicotinamide riboside (NRH) as the electron donors. In addition to the well-documented action in reducing quinone compounds and preventing the formation of reactive oxygen species, NQO enzymes, especially NQO1 also possess other important biological activities. These include anti-inflammatory effects, direct scavenging of superoxide anion radicals, and stabilization of p53 and other tumor suppressors. Recently, multiple studies in animal models demonstrated a potential role for NQO1 in protecting against cardiovascular injury and related conditions, including atherogenesis, dyslipidemia, and insulin resistance. Functional gene polymorphisms have been identified in human NQO1 gene. Studies on the association between NQO1 gene polymorphisms and susceptibility to disease development also suggested a possible involvement of NQO1 in human cardiovascular diseases and metabolic syndrome. This review is intended to summarize the recent development regarding the biochemical properties and molecular regulation of NQO1 and its potential beneficial role in cardiovascular diseases and related conditions, including metabolic syndrome.

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“…또한 NQO1효소의 NAD(P) 결합을 경쟁적으로 작용하므로 NQO1 효소 저해제 작용을 한다 [4]. 최근 인간 혈관 평활근세포에서 TNF-α에 의한 MMP-9 발현 및 분비에 NQO1의 관련성을 NQO-1 siRNA 실험을 통하여 제시하였다 [11]. Dicumarol에 의한 NQO1의 저해는 환원된 quinone의 생성 감소에 기인된 다고 제시 하고 있다 [11].…”

Section: 신장암세포인 Caki 세포에서 Pma유도 Mmp-9 활성화에 Dicumarol의 효과 확인unclassified

“…최근 인간 혈관 평활근세포에서 TNF-α에 의한 MMP-9 발현 및 분비에 NQO1의 관련성을 NQO-1 siRNA 실험을 통하여 제시하였다 [11]. Dicumarol에 의한 NQO1의 저해는 환원된 quinone의 생성 감소에 기인된 다고 제시 하고 있다 [11]. 본 연구에서는 NQO1 siRNA를 이용 한 knock-down 실험에서 dicumarol이 PMA유도의 MMP-9 활성 억제에 NQO1의 관련성을 확인 할 수 없었다 (Fig.…”

Section: 신장암세포인 Caki 세포에서 Pma유도 Mmp-9 활성화에 Dicumarol의 효과 확인unclassified

Dicumarol Inhibits PMA-Induced MMP-9 Expression through NQO1-independent manner in Human Renal Carcinoma Caki Cells

Park¹,

Kwon²

2016

Journal of Life Science

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Dicumarol is a coumarin derivative isolated from sweet clover (Melilotus alba), and has anti-coagulant activity with the inhibitory activity of NAD(P)H quinone oxidoreductase1 (NQO1). NQO1 catalyzes the two-electron reduction of quinones to hydroquinones. Dicumarol competes with NAD(P)H for binding to NQO1, resulting in the inhibition of NQO1 enzymatic activity. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. The expression of MMPs is regulated by cytokines and signal transduction pathways, including those activated by phorbol myristate acetate (PMA). However, the effects of dicumarol on metalloproteinase (MMP)-9 expression and activity are not investigated here. This study investigated whether dicumarol inhibits MMP-9 expression and activity in PMA-treated human renal carcinoma Caki cells. Dicumarol markedly inhibited the PMA-induced MMP-9 mRNA expression and MMP-9 activity. NF-κB and AP1 promoter activity, which is important in MMP-9 expression, also decreased in dicumarol-treated cells. Furthermore, dicumarol markedly suppressed the ability of PMA-mediated migration in Caki cells. When the relevance of NQO1 in the dicumarol-mediated inhibitory effect on PMA-induced MMP9 activity was elucidated, knock-down of NQO1 with siRNA was found to have no effect on PMA-induced MMP9 activity, suggesting that the stimulating effect of dicumarol on PMA-induced MMP9 activity is independent of NQO1 activity. Taken together, the present studies suggested that dicumarol may inhibit PMA-induced migration via down-regulation of MMP-9 expression and activity.

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Role of NAD(P)H:quinone oxidoreductase 1 on tumor necrosis factor-α-induced migration of human vascular smooth muscle cells

Abstract: The results of the present study demonstrate that down-regulation of NQO1 effectively suppresses TNF-alpha-induced HASMC migration through inhibition of MMP-9 expression, suggesting that NQO1 may be a potential target for the prevention of vascular disorders related to migration of VSMC.

Cited by 23 publications

References 25 publications

Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells

Downregulation of NAD(P)H:quinone oxidoreductase 1 inhibits proliferation, cell cycle and migration of cholangiocarcinoma cells

NAD(P)H:Quinone Oxidoreductase 1 and its Potential Protective Role in Cardiovascular Diseases and Related Conditions

Dicumarol Inhibits PMA-Induced MMP-9 Expression through NQO1-independent manner in Human Renal Carcinoma Caki Cells

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