N-acetylcysteine improves antitumoural response of Interferon alpha by NF-kB downregulation in liver cancer cells

Filho, Nélson Alexandre Kretzmann; Filippi-Chiela, Eduardo Cremonese; Matte, Úrsula da Silveira; Marroni, Norma Possa; Marroni, Cláudio Augusto

doi:10.1186/1476-5926-11-4

Cited by 31 publications

(23 citation statements)

References 51 publications

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“…Since NF‐κB p50 is produced as a proteolytic product of the pre‐form NF‐κB1 (p105), for qualitative purpose, the inhibitory effect of β‐eudesomol on NF‐κB (p50) expression was considered as the representative measure of NF‐κB1/p50 downregulation. Similar studies involving chemostress‐induced downregulation of NF‐κB (p65) protein have previously been employed to access the inhibitory effects of various compounds on NF‐κB expression in leukemic T and hepatic cancer cells . Taken together, the inhibitory effect of β‐eudesmol on the production of cytoprotective enzymes and stimulatory effect on the expression of key transcriptional factor proteins may be linked to the observed cytotoxicity of the compound on CL‐6 cells.…”

Section: Discussionmentioning

confidence: 85%

Growth inhibitory effect of β‐eudesmol on cholangiocarcinoma cells and its potential suppressive effect on heme oxygenase‐1 production, STAT1/3 activation, and NF‐κB downregulation

Mathema

Chai่jaroenkul

Karbwang

et al. 2017

Clin Exp Pharma Physio

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Cholangiocarcinoma (CCA) is a progressively fatal form of cancer originating from the malignant transformation of hepatic biliary cholangiocytes. The present study reports for the first time in vitro growth inhibitory activities of β-eudesmol, the bioactive sesquiterpenoid present in the rhizome of Atractylodes lancea (Thunb) DC., with respect to its underlying potential effects on heme oxygenase-1 (HO-1) production, STAT1/3 phosphorylation, and NF-κB protein expression in human CCA cell line CL-6. The cytotoxic effect of β-eudesmol on CL-6 cells was evaluated by MTT assay using normal human embryonic fibroblast (OUMS) as a control cell line. Results indicated that β-eudesmol exhibited selective cytotoxicity towards CL-6 compared to OUMS with mean (±SD) IC (concentration that inhibits cell growth by 50%) values of 166.75 ± 3.69 and 240.01 ± 16.54 μmol/L, respectively. In addition, it also significantly suppressed colony forming and wound healing ability of CL-6 cells in a concentration-dependent manner. Western blot analysis indicated that β-eudesmol treatment resulted in significant suppression of HO-1 production in CL-6 cells. Its inhibitory effects on the phosphorylation of STAT1/3 proteins and expression of NF-κB (p65 and p50) proteins were concentration-dependent. Taken together, these results suggest that β-eudesmol exerts significant growth inhibitory activity on CL-6 cells that may be linked to its inhibitory effect on the production of HO-1, phosphorylation of STAT1/3, and expression of major NF-κB proteins.

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Section: Discussionmentioning

confidence: 85%

Growth inhibitory effect of β‐eudesmol on cholangiocarcinoma cells and its potential suppressive effect on heme oxygenase‐1 production, STAT1/3 activation, and NF‐κB downregulation

Mathema

Chai่jaroenkul

Karbwang

et al. 2017

Clin Exp Pharma Physio

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“…Interestingly, the cytokines stimulation did not significantly affect total NF‐κB expression in CL‐6 cells, but atractylodin treatment moderately downregulated the key NF‐κB proteins in a dose‐dependent manner. Chemical‐induced down‐regulation of the p65 NF‐κB protein has previously been used to investigate the collective inhibitory effect of various chemicals on NF‐κB expression in hepatic cancer cells . The baseline level of the p100 NF‐κB protein was undetectable (data not shown), which may be due to the altered or abnormally high levels of phosphorylation‐dependent ubiquitination and processing of p100 protein in CL‐6 cells.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic activity and molecular targets of atractylodin in cholangiocarcinoma cells

Mathema

Chai่jaroenkul

Na‐Bangchang

2019

Journal of Pharmacy and Pharmacology

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Objectives To evaluate the cytotoxic activity of atractylodin and its potential effects on heme oxygenase (HO)‐1 production, STAT1/3 phosporylation and major NF‐κB protein expression in the cholangiocarcinoma‐associated cell line CL‐6. Methods Standard MTT assay was used for accessing antiproliferative activity on CL‐6 cells. Normal human embryonic fibroblast (OUMS) cell was taken as control cell line. Colony formation and wound healing assay were conducted to access the effects of atractylodin on cell proliferation and directional migration activity of CL‐6 cells. Western blot was used for evaluating levels of protein expression and phosphorylation. Key findings Atractylodin exhibited selective cytotoxicity towards CL‐6 as compared with OUMS with IC50 of 216.8 (212.4‐233.8) and 351.2 (345.7‐359.5) μm [median (range)], respectively. Exposure to the compound dose‐dependently inhibited colony formation ability and decreased wound closure potential of CL‐6 cells. Atractylodin treatment suppressed HO‐1 production in CL‐6 cells. It dose‐dependently inhibited STAT1/3 protein phosphorylation and moderately inhibited NF‐κB (p50), NF‐κB (p52), and NF‐κB (p65) protein expression in both dose‐ and time‐dependent manner. Conclusions Atractylodin exerts significant cytotoxic activity against CL‐6 cells which may be linked to its suppressive effect on HO‐1 production, STAT1/3 phosphorylation and expression of key NF‐κB proteins.

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“…Activation of NF-κB in response to various signals, including IL-1, TNF and H2O2 can be inhibited by NAC treatment, suggesting that ROS are common signaling modulators [258] . Moreover, NAC was found to enhance the effect of IFN-α on liver tumor cells through inhibition of NF-κB [259] . On the other hand, some studies suggested that NAC inhibits the upstream IKK activation induced by TNF-α [260] .…”

Section: Of Viral Infectionsmentioning

confidence: 99%

Inflammatory and oxidative stress in rotavirus infection

Guerrero¹,

Acosta²

2016

WJV

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Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virusassociated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines. Core tip: Rotavirus entry into the host cell requires cell surface molecules providing binding, chaperoning and oxido-reducing functions. Sialic acid/integrin α2β1, heat shock cognate protein 70 and protein disulfide isomerase (PDI) seem to perform these functions. Recently, the cell surface oxido-reduction activity based at least on PDI has been highlighted as a potential determinant of the conformational changes that are required by viral structural proteins in order to facilitate virus entry. The rotavirus-induced oxidative stress and inflammatory signaling is an attractive target for therapeutic intervention as antioxidant and anti-inflammatory treatment has Submit a

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N-acetylcysteine improves antitumoural response of Interferon alpha by NF-kB downregulation in liver cancer cells

Cited by 31 publications

References 51 publications

Growth inhibitory effect of β‐eudesmol on cholangiocarcinoma cells and its potential suppressive effect on heme oxygenase‐1 production, STAT1/3 activation, and NF‐κB downregulation

Growth inhibitory effect of β‐eudesmol on cholangiocarcinoma cells and its potential suppressive effect on heme oxygenase‐1 production, STAT1/3 activation, and NF‐κB downregulation

Cytotoxic activity and molecular targets of atractylodin in cholangiocarcinoma cells

Inflammatory and oxidative stress in rotavirus infection

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