Melatonin prevents human pancreatic carcinoma cell PANC‐1‐induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression

Cui, Peilin; Yu, Minghua; Peng, Xing‐Chun; Dong, Lei; Yang, Zhao-Xu

doi:10.1111/j.1600-079x.2011.00933.x

Cited by 50 publications

(56 citation statements)

References 36 publications

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“…Cristofanon et al described that melatonin can induce NF-κB activation in U937 cells and suggested a possible involvement for ROS induced by melatonin (Cristofanon et al, 2009). In contrast to cancer cells, melatonin did not induce cytotoxicity in noncancer cells, including human umbilical vein endothelial cells (Cui et al, 2012), primary hepatocytes (Kojima et al, 1997), neuronal stem cells (Fu et al, 2011), and HT22, a mouse hippocampal cell line (Rodriguez et al, 2013). A further study reported that in human platelets, melatonin considerably increased the generation of intracellular ROS and Ca…”

Section: Prooxidant Actions 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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Section: Prooxidant Actions Of Melatoninmentioning

confidence: 99%

Prooxidant effects of melatonin: a brief review

Munik¹,

Ekmekçioğlu²

2015

Turk J Biol

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“…However, the mechanisms of melatonin's antiangiogenic in any tumor including NSCLC are still unclear. Numerous studies have documented that melatonin exhibits antiangiogenic actions, in part, by downregulating VEGF and HIF-1α in several cancers via different mechanisms; the cancer types included breast [16, 149], prostate [150–152], colon [153, 154], liver [155], and pancreatic cancer [156, 157]. These studies may provide reference for the future work in the NSCLC research field.…”

Section: Potential Directionsmentioning

confidence: 99%

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

Yang

Fan

et al. 2016

Oncotarget

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Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an indoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC.

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“…To assess the effect of melatonin on hypoxia-induced HUVEC migration, we treated cells with different doses of melatonin [8,20] and measured the migration rate by wound closure assay. As shown in Figure 1A, an upregulation of HUVEC migration occurred after exposure to hypoxia; the cell migratory ability decreased gradually with increasing doses of melatonin.…”

Section: Resultsmentioning

confidence: 99%

“…For the cell migration assay, the cell wound closure assay was performed as previously described [20]. Briefly, a scratch was made in the monolayer of HUVEC cells by using a 10-µL pipette tip.…”

Section: Methodsmentioning

confidence: 99%

Melatonin Suppresses Hypoxia-Induced Migration of HUVECs via Inhibition of ERK/Rac1 Activation

Yang

Zheng

et al. 2014

IJMS

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Melatonin, a naturally-occurring hormone, possesses antioxidant properties and ameliorates vascular endothelial dysfunction. In this study, we evaluate the impact of melatonin on the migratory capability of human umbilical vein endothelial cells (HUVECs) to hypoxia and further investigate whether ERK/Rac1 signaling is involved in this process. Here, we found that melatonin inhibited hypoxia-stimulated hypoxia-inducible factor-1α (HIF-1α) expression and cell migration in a dose-dependent manner. Mechanistically, melatonin inhibited Rac1 activation and suppressed the co-localized Rac1 and F-actin on the membrane of HUVECs under hypoxic condition. In addition, the blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1-T17N suppressed HIF-1α expression and cell migration in response to hypoxia, as well, but constitutive activation of Rac1 mutant Rac1-V12 restored HIF-1α expression, preventing the inhibition of melatonin on cell migration. Furthermore, the anti-Rac1 effect of melatonin in HUVECs appeared to be associated with its inhibition of ERK phosphorylation, but not that of the PI3k/Akt signaling pathway. Taken together, our work indicates that melatonin exerts an anti-migratory effect on hypoxic HUVECs by blocking ERK/Rac1 activation and subsequent HIF-1α upregulation.

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Melatonin prevents human pancreatic carcinoma cell PANC‐1‐induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression

Cited by 50 publications

References 36 publications

Prooxidant effects of melatonin: a brief review

Prooxidant effects of melatonin: a brief review

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

Melatonin Suppresses Hypoxia-Induced Migration of HUVECs via Inhibition of ERK/Rac1 Activation

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