Anesthetic agent etiomidate induces apoptosis in N2a brain tumor cell line

Chen, Hongtao; Zhou, Jun; Fan, Yu; Lei, Chunliang; Li, Baojin; Fan, Li; Xu, Li; Xu, Ming; Hu, Xiu‐Qin; Yu, Zhiying

doi:10.3892/mmr.2018.9298

Cited by 5 publications

(5 citation statements)

References 33 publications

(27 reference statements)

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“…Etomidate has less effect on immune function in patients with lung adenocarcinoma (29). In addition, etomidate induced apoptosis in N2a brain tumor cell line (30). In our previous study, we demonstrated that etomidate, citosol and propofol induced the expression of apoptosis-related genes, inhibited the expression of cell growth genes and altered the expression of apoptosis-related proteins in a mouse leukemia cell line (RAW264.7) (12)(13)(14)(15).…”

Section: Discussionmentioning

confidence: 94%

Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells

Chu

Chung

et al. 2018

Anticancer Res

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Background/Aim: Etomidate, an intravenous anesthetic, has been shown to have anticancer effects, including induction of cell-cycle arrest and apoptosis. However, to our knowledge, there are no reports about the anti-metastasis effects of etomidate on A549 human lung adenocarcinoma cells. Materials and Methods: The cell viability, cell adhesion, gelatin zymography assay, transwell migration and invasion assay, and western blotting analysis were used to investigate the effects of etomidate on A549 cells. Results: In our study, etomidate showed low cytotoxicity, inhibited cell adhesion, and suppressed the migration and invasion in A549 cells. The activity of matrix metallopeptidase 2 (MMP2) was reduced by 48 h treatment of etomidate. Results of western blotting analysis indicated that etomidate downregulated the expression of protein kinase C, MMP7, MMP1, MMP9, and p-p-38, but up-regulated that of RAS, phosphoinositide 3-kinase, and phosphor-extracellular-signal related kinase after 24 and 48 h treatment, in A549 cells. Conclusion: Etomidate suppressed the migration and invasion of lung adenocarcinoma A549 cells via inhibiting the expression of MMP1, MMP2, MMP7 and MMP9, and provides potential therapeutic targets for lung cancer treatment.Cancer has been the leading cause of death in Taiwan for 31 years (1). According to the International Agency for Research on Cancer, it accounted for 1.8 million deaths (around 18.4% of all deaths) in 2018 worldwide (2). Since 90% of patients with cancer die due to metastases (3), inhibition of metastasis is a major concern in the care of such patients. Although surgery is a major approach for cancer removal, intraoperative manipulation of cancer tissues may release cancer cells into the vascular and lymphatic circulation or to neighboring tissues (4, 5). In those with a normal immune status, macrophage, dendritic cells, natural killer cells and T-cells have the ability to identify and to destroy cancer cells in the circulation. However, compromised immunity blocks these abilities and may lead to recurrence or progression of malignant diseases (6-9). Stressful perioperative events such as pain, surgery, transfusion, hypothermia, hypotension, electrolyte imbalance, and shock, inhalation anesthetics, and morphine depress immunological function can increase the incidence of cancer cell metastasis and cancer recurrence rate in patients treated for cancer with surgery (10, 11).

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Section: Discussionmentioning

confidence: 94%

Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells

Chu

Chung

et al. 2018

Anticancer Res

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“…Previous studies have shown that etomidate impeded migration and invasion of A549 lung adenocarcinoma cells by inhibiting the expression of matrix in vivo 36: 2722-2729 (2022) metalloproteinases 1, 2, 7 and 9 (35). Furthermore, etomidate exerted antiproliferative effects on adrenocortical carcinoma (36) and induced apoptosis in neuroblastoma (37). In contrast, Deng et al showed that etomidate increased migration of colon carcinoma cells via the phosphatidylinositol-4,5-bisphosphate 3-kinase-AKT serine/ threonine kinase 1 pathway (38).…”

Section: Discussionmentioning

confidence: 97%

Effect of Propofol and Etomidate on the Proliferation, Cell-cycle Distribution, Apoptosis and Necrosis of Pancreatic Tumour Cells

Malsy

Graf

Hofer

et al. 2022

In Vivo

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Background/Aim: The influence of surgical interventions and anaesthesiological procedures on tumour progression was investigated as early as the 1920s. In current cancer management, the perioperative phase is increasingly being considered a vulnerable period with an increased risk of tumour cell dissemination due to medication, surgical manipulation, and immunosuppression. The extent to which narcotics administered in the perioperative setting influence the oncological outcomes of patients with pancreatic cancer is still unclear. Materials and Methods: To investigate the effect of propofol and etomidate on the proliferation, cellcycle distribution, apoptosis, and necrosis of pancreatic tumour cells in vitro, PaTu 8988t and Panc-1 pancreatic cancer cells were treated with 0-1,000 μM propofol or etomidate for 24 h each. Cell proliferation was measured with enzyme-linked immunosorbent-bromodeoxyuridine assay. The apoptosis rate was analysed with annexin V staining and the cell-cycle distribution with flow cytometry. Results: Propofol at 1,000 μM induced apoptosis and inhibited cell proliferation. The cell cycle showed an increased S-phase and reduced cells in the G 1 -phase. At 100 μM, propofol significantly inhibited proliferation of the pancreatic cancer cell line PaTu 8988t and reduced cells in the G 2 -phase in the cell cycle. Etomidate had no effects on cell-cycle distribution, proliferation, apoptosis, and necrosis at the concentrations used. Conclusion: In this study, propofol was shown to have

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“…Previous studies have shown that ETO exerts antioxidant, anti-inflammatory, antitumor and antiplatelet aggregation effects ( 24 , 25 ). For example, ETO could reduce the proliferation, migration and invasion of human adrenocortical cancer cells ( 9 ) and induce the apoptosis of N2a brain tumor cells ( 10 ). In lung cancer, one previous study demonstrated that ETO can effectively attenuate the proliferation and migration of A549 cells, supporting the notion of antitumor effects of ETO on NSCLC ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that ETO exerts an inhibitory role in several types of cancer. For example, it has been demonstrated that ETO could attenuate the proliferation of human adrenocortical cancer cells ( 9 ) and enhance the apoptosis of N2a neuroblastoma cells ( 10 ). In addition, ETO was found to significantly inhibit the migratory and invasive abilities of NSCLC cells ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Etomidate inhibits cell proliferation and induces apoptosis in A549 non‑small cell lung cancer cells via downregulating WWP2

Zhang

Yin

et al. 2021

Exp Ther Med

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Etomidate (ETO) is a commonly used intravenous anesthetic that has been reported to exert a tumor suppressive effect in several types of cancer. The present study aimed to investigate the effect of ETO on cell proliferation and apoptosis in non-small cell lung cancer (NSCLC) cells and elucidate its potential mechanism of action. Therefore, Cell Counting Kit-8 assay was performed to evaluate the effect of different concentrations of ETO (0, 1, 2 or 3 µg/ml) on A549 cell viability. In addition, the possible interaction between ETO and WW domain containing E3 ubiquitin protein ligase 2 (WWP2) was predicted using the STITCH database. Additionally, a stable WWP2-overexpressing A549 cell line was constructed by transfecting A549 cells with the pcDNA3.1-WWP2 plasmid. Cell proliferation and apoptosis were assessed using colony formation and TUNEL assays, respectively. The mRNA and protein expression levels of the apoptosis-related proteins Bcl-2, Bax, caspase 3 and cleaved-caspase 3 were determined by reverse transcription-quantitative PCR and western blotting. In addition, the expression and phosphorylation levels of proliferation-associated genes (PCNA and Ki-67) and proteins in the PI3K/Akt pathway were analyzed by western blotting. The results showed that treatment with ETO attenuated the cell viability and proliferation of A549 cells. ETO also promoted cell apoptosis and decreased the expression of the anti-apoptotic protein Bcl-2, whilst increasing that of pro-apoptotic proteins Bax and cleaved caspase 3 in a dose-dependent manner. Furthermore, ETO was found to negatively regulate the expression of WWP2, such that WWP2 overexpression reversed the potentiating effects of ETO on cell apoptosis. In addition, ETO promoted the expression of PTEN and reduced the phosphorylation levels of the PI3K/AKT pathway-related proteins. These effects aforementioned could also be reversed by WWP2 overexpression. Therefore, data from the present study suggest that ETO can attenuate the progression of NSCLC through by the PI3K/AKT pathway, specifically by targeting WWP2. These findings may provide a novel target for the treatment of NSCLC.

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Anesthetic agent etiomidate induces apoptosis in N2a brain tumor cell line

Cited by 5 publications

References 33 publications

Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells

Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells

Effect of Propofol and Etomidate on the Proliferation, Cell-cycle Distribution, Apoptosis and Necrosis of Pancreatic Tumour Cells

Etomidate inhibits cell proliferation and induces apoptosis in A549 non‑small cell lung cancer cells via downregulating WWP2

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