Melatonin Inhibits the Migration of Human Lung Adenocarcinoma A549 Cell Lines Involving JNK/MAPK Pathway

Zhou, Qing; Gui, Shuyu; Zhou, Qing; Wang, Yuan

doi:10.1371/journal.pone.0101132

Cited by 69 publications

(70 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, the p38 and JNK pathways appeared to be activated at therapeutic concentrations of melatonin in a gastric adenocarcinoma cell line. However, it has been shown that melatonin significantly inhibits the migration of A549 cells, which may be associated with the downregulation of the JNK/MAPK signaling pathway (46). The results of the current study indicate that the activation of p38 and JNK by melatonin initiates a molecular proliferative response in SGC7901 cells.…”

Section: Discussionmentioning

confidence: 48%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 48%

“…A decrease in the level of the p-p65/p65 protein in SGC7901 cells treated with 2 mM melatonin was observed at 12 h (P<0.05), with a maximal significantly decreased level at 24 h of ~0. 46 fold compared with that of the control cells (P<0.01; Fig. 4B).…”

Section: Resultsmentioning

confidence: 85%

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

View full text Add to dashboard Cite

show abstract

“…The ability of tumor cells to migrate is an important prerequisite for tumor dissemination and metastasis (15,39). A number of studies have additionally indicated that melatonin may have antimetastatic properties and may be able to reduce migration and invasiveness in certain types of cancer, including glioblastoma (22,25), lung (26) and breast cancer cells (27)(28)(29). According to Ortíz-López et al (28) melatonin inhibits the migration process and cell invasion in breast cancer cells via the rho-associated-1 protein, by modulating the dynamic cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental results have additionally indicated that melatonin may be capable of reducing migration and invasiveness in glioblastoma (22,25), lung (26) and breast cancer cells (27)(28)(29). However, much remains to be elucidated regarding the antimetastatic properties of melatonin in HCC cells.…”

Section: Introductionmentioning

confidence: 99%

Effects of melatonin on HIF-1α and VEGF expression and on the invasive properties of hepatocarcinoma cells

et al. 2016

View full text Add to dashboard Cite

Abstract. Liver cancer is the sixth most commonly occurring cancer globally, and the main histological type is hepatocellular carcinoma. This type of neoplasia has a poor prognosis due to a high rate of recurrence and intrahepatic metastasis, which are closely are closely associated with the angiogenic process. Vascular endothelial growth factor (VEGF), which is under the control of hypoxia inducible factor-1α (HIF-1α), stimulates the proliferation of endothelial cells and increases cell permeability, promoting the growth, spread and metastasis of tumors. Melatonin, the main hormone secreted by the pineal gland, may have a significant role in tumor suppression and has demonstrated antiangiogenic and antimetastatic effects. The aim of the present study was to analyze the cell viability, migration and invasion, as well as the expression of proangiogenic proteins VEGF and HIF-1α, in HepG2 hepatocarcinoma cells, following treatment with melatonin. Cells were cultured and cell viability was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of proangiogenic proteins VEGF and HIF-1α, under conditions of normoxia and hypoxia, was verified using immunocytochemistry and quantified by densitometry. The analysis of the processes of cell migration and invasion was performed in a Boyden chamber. The MTT assay revealed a reduction in cell viability (P=0.018) following treatment with 1 mM melatonin for 24 h. The expression of proangiogenic proteins VEGF and HIF-1α was reduced in cells treated with 1 mM melatonin for 24 h in normoxic (P<0.001) and hypoxic (P<0.001) conditions, compared with the control group and with induced hypoxia alone. The rate of cell migration and invasion was additionally reduced in cells treated with 1 mM melatonin for 48 h when compared with the control group (P=0.496). The results of the present study suggest that melatonin may have an antiproliferative, antiangiogenic and antimetastatic role in hepatocarcinoma cells and may present a novel therapeutic option for the treatment of liver cancer.

show abstract

“…Each group of MAPKs is activated by a distinct kinase cascade in which a MAP3K or MEKK phosphorylates and activates a downstream dual-specificity MAP2K or MEK, which in turn stimulates MAPK activity through dual phosphorylation of threonine and tyrosine residues within a conserved tripeptide motif (Thr-X-Tyr). Phosphorylation of these threonine and tyrosine residues on MAPKs results in a conformational change that increases substrate accessibility and enhances catalysis (Zhou et al 2014). Activation of ERK is through phosphorylation by MEK (MAPK/ERK kinase) 1/2 in response to various cytokines and growth factors and mediates mitogenic and antiapoptotic signals primarily, whereas members of the JNK and p38 family of MAPKs were identified originally as mediators of cellular stress and are activated by MKK4/MKK7 and MKK3/MKK6, respectively (Lei et al 2014;Moon and Park 2014;Yao et al 2014;Zhou et al 2014).…”

Section: Introductionmentioning

confidence: 99%

NT-3 attenuates the growth of human neuron cells through the ERK pathway

Jiang

2014

Cytotechnology

View full text Add to dashboard Cite

Spinal cord injury is a devastating health problem that affects thousands of individuals each year. The neurons were destroyed. NT-3 is a recently discovered neurotrophin. This study sought to understand the potential involvement of MAPKs in NT-3-mediated growth inhibition of human neurons. We applied different concentrations of NT-3 and observed the growth rate of the cells and the changes in the phosphorylation state of the MAPKs ERK1/2, JNK and p38. This study discovered that NT-3-induced HNC growth was promoted primarily by phosphorylated ERK1/2, and that this phosphorylation, as well p90 rsk phosphorylation, was mediated by TrkC. The ERK1/2 pathway is known to play an essential role in the NT-3-mediated growth of human neurons. In conclusion, our study suggests that NT-3 promotes the growth of human neurons cells primarily through the TrkC/ERK pathway.

show abstract

Melatonin Inhibits the Migration of Human Lung Adenocarcinoma A549 Cell Lines Involving JNK/MAPK Pathway

Cited by 69 publications

References 56 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

Effects of melatonin on HIF-1α and VEGF expression and on the invasive properties of hepatocarcinoma cells

NT-3 attenuates the growth of human neuron cells through the ERK pathway

Contact Info

Product

Resources

About