Inhibition of matrix metalloproteinase‐9 and nuclear factor kappa <scp>B</scp> contribute to melatonin prevention of motility and invasiveness in <scp>H</scp>ep<scp>G</scp>2 liver cancer cells

Ordóñez, Raquel; Carbajo-Pescador, Sara; Prieto-Domínguez, Néstor; García‐Palomo, Andrés; González‐Gallego, Javier; Mauriz, José L.

doi:10.1111/jpi.12092

Cited by 99 publications

(97 citation statements)

References 77 publications

(113 reference statements)

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“…Melatonin has also been reported to exhibit a protective role against diabetic neuropathy via the NF-κB signaling pathway (37). However, another study demonstrated that melatonin significantly suppressed interleukin-1β-induced NF-κB translocation and transcriptional activity in human hepatocellular HepG2 cells (17). The inhibitory action of melatonin on NF-κB leads to an anti-inflammatory and pro-apoptotic effect on cancer cell lines (38,39).…”

Section: Discussionmentioning

confidence: 96%

“…Several studies have revealed that melatonin is useful for the prevention of cancer (13,14). The antitumor ability of melatonin may be mediated by numerous mechanisms, including the activation of antioxidative stress, inhibition of migration and induction of apoptosis (15)(16)(17). Melatonin has also been demonstrated to suppress the growth, migration and invasion of SGC7901 gastric cancer cells in vitro (18), and to exert an apoptotic effect in the hepatocellular carcinoma HepG2 cell line (19).…”

Section: Introductionmentioning

confidence: 99%

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Melatonin treatment induces apoptosis through regulating the nuclear factor-κB and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells

et al. 2017

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Abstract. Melatonin, which is synthesized by the pineal gland and released into the blood, exhibits antitumor properties. However, the mechanisms underlying these effects, particularly in stomach cancer, remain unknown. In the present study, the effect of melatonin on the nuclear factor (NF)-κB signaling pathway and the mitogen-activated protein kinase signaling pathway, involving p38 and c-Jun-N-terminal kinase (JNK), were investigated in SGC7901 gastric cancer cells. In addition, the effect of melatonin on the survival, migration and apoptosis of these cells was investigated in vitro in order to evaluate the use of melatonin for the treatment of gastric cancer. The results of the present study revealed that melatonin decreased the viability and migration of SGC7901 cells. Furthermore, melatonin induced apoptosis. Melatonin was identified to elevate the expression levels of phosphorylated (p)-p38 and p-JNK protein, and decrease the expression level of nucleic p-p65. These results suggest that the protein levels of p65, p38 and JNK are associated with the survival of SGC7901 cells following treatment with melatonin. The optimal concentration of melatonin was demonstrated to be 2 mM, which significantly induced apoptosis following a 24 h treatment period. These findings suggest that conflicting growth signals in cells may inhibit the efficacy of melatonin in the treatment of gastric cancer. Therefore, adjunct therapy would be required to improve the efficacy of melatonin in the treatment of cancer. IntroductionGastric carcinoma is one of the most common types of malignancy, worldwide (1). In Asia, patients tend to be diagnosed at an average age of 66.8 years, and exhibit poor rates of survival (1). Gastric cancer is a refractory cancer and the third-leading cause of cancer-associated mortality in China (2). Gastric adenocarcinoma is the predominant type of gastric cancer and has limited treatment options (3). The typical treatments for gastric cancer, surgery and chemotherapy, only partially improve the overall survival of patients with this disease (4,5). Therefore, more effective drugs or comprehensive therapies are required (6).Melatonin is an indole hormone secreted by the pineal gland and was first identified in 1958 (7). Melatonin serves a significant role in a wide variety of biological processes, including sleep, immunomodulation, anti-inflammation and antioxidative stress (8-11). In addition, melatonin is an anticancer hormone and a potential target for cancer treatments (12). Several studies have revealed that melatonin is useful for the prevention of cancer (13,14). The antitumor ability of melatonin may be mediated by numerous mechanisms, including the activation of antioxidative stress, inhibition of migration and induction of apoptosis (15)(16)(17). Melatonin has also been demonstrated to suppress the growth, migration and invasion of SGC7901 gastric cancer cells in vitro (18), and to exert an apoptotic effect in the hepatocellular carcinoma HepG2 cell line (19). Additionally, the use of melatonin h...

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Melatonin treatment induces apoptosis through regulating the nuclear factor-κB and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells

et al. 2017

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“…Some experimental models of tissue damage demonstrate that melatonin acts protectively by reducing oxidative stress and lipid peroxidation (Pieri et al, 1995;Reiter et al, 1998). Furthermore, melatonin exerts anticancer activities through either cytostatic mechanisms or cytotoxic actions by inhibiting cell proliferation and/or reducing viability in several cancer cell lines, including rat pancreatic tumor cells (Gonzalez et al, 2011), human hepatocellular carcinoma cells (Ordoñez et al, 2014), human B-lymphoma cells (Trubiani et al, 2005), human myeloid HL-60 leukemia cells (Rubio et al, 2007), and human neuroblastoma cancer cells (Garcia-Santos et al, 2006).…”

Section: Antioxidative Effects Of Melatoninmentioning

confidence: 99%

Prooxidant effects of melatonin: a brief review

Munik¹,

Ekmekçioğlu²

2015

Turk J Biol

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IntroductionMelatonin, chemically N-acetyl-5-methoxytryptamine, was primarily isolated from bovine pineal glands and its structure was first identified in 1958 (Lerner et al., 1958). This indolamine was later discovered to be also present or synthesized in extrapineal tissues such as the retina, gastrointestinal tract, Harderian gland, testes, and lymphocytes (Reiter et al., 2013). Due to the fact that melatonin possesses hydrophilic and lipophilic characteristics, its lipophilic ability enables it to penetrate all biological membranes, including the blood-brain barrier (Reiter et al., 1997). Generally, melatonin derives from the essential amino acid tryptophan by a multistep enzymatic reaction chain, including tryptophan 5-hydroxylation, decarboxylation, N-acetylation, and O-methylation. Furthermore, melatonin can be synthesized via O-methylation of serotonin and subsequent N-acetylation of 5-methoxytryptamine, or by O-methylation of tryptophan, followed by decarboxylation and N-acetylation (Hardeland et al., 1993). From a functional perspective, melatonin is characterized as a hormone involved in the regulation of the circadian rhythm of several biological functions and it also plays an important role in immunoregulation, reproduction, sleep, and inflammatory responses (Hardeland and Fuhrberg, 1996;Reiter et al., 2000). MT 1 and MT 2 are two well-characterized G protein-coupled plasma membrane melatonin receptors, which are activated by melatonin and regulate multiple cellular and physiological functions, including neuronal activity, arterial vasoconstriction, cell proliferation, immune responses, reproduction, and metabolic functions (Stankov and Reiter, 1990;Dubocovich and Markowska, 2005;Ekmekçioğlu, 2006Ekmekçioğlu, , 2014. In addition, melatonin has high-affinity binding for nuclear receptors ROR/RZR, which operate as transcriptional activators, and it also interacts with other intracellular proteins, like quinone reductase-2 (or MT 3 ) and calmodulin (Reppert et al., 1994;Wiesenberg et al., 1998). For the regulation of gene expression, it has been proposed that ROR/RZR work in cooperation with the plasma membrane receptors MT 1 /MT 2 (Carrillo-Vico et al., 2005). Regarding the regulation of the cellular redox status, melatonin possibly interacts with quinone reductase, even though the detailed role of this interaction remains poorly understood .Melatonin and calmodulin possess low-affinity interaction, which may relate to their antioxidant actions, as well as other signaling processes (Luchetti et al., 2010). Various studies describe melatonin and its derivatives as broad-spectrum antioxidants, related to their ability to Abstract: Melatonin acts classically through the widely expressed G protein-coupled membrane receptors MT 1 and MT 2 , respectively. The functional role of the MT receptors is not fully clear with multiple effects, such as effects on the circadian, reproductive, immune, cardiovascular, and intestinal systems, being suggested. In addition to receptor-mediated effects, melatonin also acts ...

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“…A few report suggested that melatonin prevents gastrointestinal cancer development by modulation of MMP functions. Melatonin induces apoptosis and reduces invasiveness of HepG2 cells in vitro through TIMP-1 upregulation and attenuation of MMP-9 activity via NFκB signal pathway [196] . Rudra et al [192] reported that melatonin reduces MMP-9 activity in AGS cell line and binds directly to its active site.…”

Section: Other Promising Dietary Antioxidantsmentioning

confidence: 99%

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

Verma

Kesh

Ganguly

et al. 2014

WJBC

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teinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteinerich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/ anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows. AbstractThe process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metallopro-

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Inhibition of matrix metalloproteinase‐9 and nuclear factor kappa B contribute to melatonin prevention of motility and invasiveness in HepG2 liver cancer cells

Cited by 99 publications

References 77 publications

Melatonin treatment induces apoptosis through regulating the nuclear factor-κB and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells

Melatonin treatment induces apoptosis through regulating the nuclear factor-κB and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells

Prooxidant effects of melatonin: a brief review

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

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