Nitric oxide inhibits gastric cancer cell growth through the modulation of the Akt pathway

Sang, Jianrong; Chen, Yongchang; Yan, Tao

doi:10.3892/mmr.2011.535

Cited by 25 publications

(25 citation statements)

References 23 publications

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“…1B, the proliferation of HepG2 cells was significantly inhibited by NO, with a greater degree of suppression when increasing concentrations of SNP were used. This observation is consistent with a previous study, which demonstrated that NO generated by treatment with SNP inhibited the cell proliferation of gastric cancer cells in a concentration-dependent manner (16).…”

Section: Discussionsupporting

confidence: 82%

“…NO is known to be involved in diverse processes in numerous physiological and pathophysiological conditions; previous studies have suggested that NO can exert a negative effect on the (10,(12)(13)(14)(15)(16)(17)(18). However, studies concerning the effects of NO on HCC cells are rare.…”

Section: Discussionmentioning

confidence: 94%

“…These data indicate that NO arrested HepG2 cells in the G 1 phase. Sang et al observed that SNP-derived NO inhibited the proliferation of gastric cancer cells by blocking the conversion from the G 1 to the S phase, and the G 1 arrest was mediated through the regulation of cell cycle-related proteins, which was likely to be associated with the inactivation of Akt signaling (16). These results suggest that NO can regulate cell cycle transition, thereby suppressing cancer cell proliferation.…”

mentioning

confidence: 84%

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Effects of nitric oxide on the biological behavior of HepG2 human hepatocellular carcinoma cells

Zhou

Zhang

2016

Experimental and Therapeutic Medicine

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Abstract. Many studies have found the function of nitric oxide (NO) in cancer as a pro-neoplastic vs. an anti-neoplastic effector, but the role of NO in hepatocellular carcinoma (HCC) remains unclear. The present study aimed to investigate the effects of nitric oxide (NO) on the biological behavior of the human hepatocellular carcinoma cell line HepG2. HepG2 cell was cultured in vitro and treated with or without sodium nitroprusside (SNP), a NO donor. Subsequently, we evaluated the effects of NO in cell proliferation, cell cycle, apoptosis, migration and invasion by MTT assay, flow cytometry, wound healing assay and Matrigel invasion assay. We demonstrate that NO significantly inhibited HepG2 cell proliferation by inducing G 0 /G 1 phase arrest in a dose-dependent manner. In addition, compared to the control group, cells treated with SNP showed obviously higher apoptosis ratios in a dose-dependent manner. Furthermore, we revealed that NO effectively inhibited the ability of migration and invasion of HepG2 cells. Taken together, our results suggested that NO has an important role in the regulation of biological behavior in HepG2 cells and the potential for use in the prevention and treatment of HCC.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 84%

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Effects of nitric oxide on the biological behavior of HepG2 human hepatocellular carcinoma cells

Zhou

Zhang

2016

Experimental and Therapeutic Medicine

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“…This was also observed by Sang et al (29). However, when combined with Ad-PKG II infection, SNP and L-arginine treatment markedly inhibited the EGF-induced activation of p-ERK1/2, suggesting that SNP and L-arginine-induced NO/cGMP production exerts an effect on the activation of ERK, but not EGFR.…”

Section: Discussionsupporting

confidence: 62%

Nitric oxide/cyclic guanosine monophosphate inducers sodium nitroprusside and L-arginine inhibit the proliferation of gastric cancer cells via the activation of type II cyclic guanosine monophosphate-dependent protein kinase

Yao

Zhu

et al. 2015

Oncology Letters

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Abstract. Nitric oxide (NO) may activate soluble guanylyl cyclase (sGC), resulting in the increase of intracellular cyclic guanosine monophosphate (cGMP), a key molecule in the activation of type II cGMP-dependent protein kinase (PKG II). In our previous study, the membrane-permeable cGMP analogue 8-pCPT-cGMP was used to activate PKG II. The aim of the present study was to investigate whether NO/sGC-induced endogenous cGMP is able to activate PKG II and induce the corresponding effects. In the AGS gastric cancer cell line, the expression of PKG II was increased by infecting the cells with an adenoviral construct encoding PKG II cDNA (Ad-PKG II) and the activation of PKG II was induced by 8-pCPT-cGMP (positive control), the NO donor sodium nitroprusside (SNP) and the NO precursor L-arginine. ELISA was performed to detect the concentration of cGMP in AGS cells and the Cell Counting Kit-8 was used to analyze the proliferation of differently treated cells. Western blot analysis was used to detect the expression and phosphorylation of associated proteins. The results demonstrated that the level of cGMP was increased in cells treated with the NO donor or precursor. There was an obvious increase of Ser239 phosphorylation of the vasodilator-stimulated phosphoprotein, representing the increase in the activity of PKG II. The epidermal growth factor (EGF)-induced proliferation of AGS cells was inhibited by infection with Ad-PKG II and treatment with SNP or L-arginine. In addition, EGF-induced tyrosine phosphorylation of the EGF receptor (EGFR) and tyrosine/serine phosphorylation of extracellular signal-regulated kinase (ERK) were also inhibited by infection with Ad-PKG II and treatment with the NO donor or precursor. These data indicated that NO donors and precursors may activate the expression of PKG II, thereby blocking EGF-initiated signaling of the mitogen-activated protein kinase/ERK pathway and inhibiting EGF-induced proliferative activity through preventing the phosphorylation of EGFR at Tyr1068.

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“…The degree of inhibition of proliferation and migration capacity was directly proportional to the concentration of the NO donor (Zhou et al, 2016). Similar dose dependent inhibitory results on cellular proliferation have been observed in gastric cancer cells that were treated with an NO donor (Sang et al, 2011). Expression of NO was also observed to block cellular migration of HeLa cells and endothelial cells by blunting the phosphorylation of Akt/PKB (Bulotta et al, 2009).…”

Section: Introductionsupporting

confidence: 75%

Nitric Oxide Modulates Postnatal Bone Marrow-Derived Mesenchymal Stem Cell Migration

Fuseler

Valarmathi

2016

Front. Cell Dev. Biol.

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Nitric oxide (NO) is a small free-radical gas molecule, which is highly diffusible and can activate a wide range of downstream effectors, with rapid and widespread cellular effects. NO is a versatile signaling mediator with a plethora of cellular functions. For example, NO has been shown to regulate actin, the microfilament, dependent cellular functions, and also acts as a putative stem cell differentiation-inducing agent. In this study, using a wound-healing model of cellular migration, we have explored the effect of exogenous NO on the kinetics of movement and morphological changes in postnatal bone marrow-derived mesenchymal stem cells (MSCs). Cellular migration kinetics and morphological changes of the migrating MSCs were measured in the presence of an NO donor (S-Nitroso-N-Acetyl-D,L-Penicillamine, SNAP), especially, to track the dynamics of single-cell responses. Two experimental conditions were assessed, in which SNAP (200 μM) was applied to the MSCs. In the first experimental group (SN-1), SNAP was applied immediately following wound formation, and migration kinetics were determined for 24 h. In the second experimental group (SN-2), MSCs were pretreated for 7 days with SNAP prior to wound formation and the determination of migration kinetics. The generated displacement curves were further analyzed by non-linear regression analysis. The migration displacement of the controls and NO treated MSCs (SN-1 and SN-2) was best described by a two parameter exponential functions expressing difference constant coefficients. Additionally, changes in the fractal dimension (D) of migrating MSCs were correlated with their displacement kinetics for all the three groups. Overall, these data suggest that NO may evidently function as a stop migration signal by disordering the cytoskeletal elements required for cell movement and proliferation of MSCs.

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Nitric oxide inhibits gastric cancer cell growth through the modulation of the Akt pathway

Cited by 25 publications

References 23 publications

Effects of nitric oxide on the biological behavior of HepG2 human hepatocellular carcinoma cells

Effects of nitric oxide on the biological behavior of HepG2 human hepatocellular carcinoma cells

Nitric oxide/cyclic guanosine monophosphate inducers sodium nitroprusside and L-arginine inhibit the proliferation of gastric cancer cells via the activation of type II cyclic guanosine monophosphate-dependent protein kinase

Nitric Oxide Modulates Postnatal Bone Marrow-Derived Mesenchymal Stem Cell Migration

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