Calprotectin (S100A8/S100A9)-induced cytotoxicity and apoptosis in human gastric cancer AGS cells: Alteration in expression levels of Bax, Bcl-2, and ERK2

Calprotectin is a heterodimeric EF-hand Ca2+ binding protein that is typically released by infiltrating polymorphonuclear leukocytes and macrophages. This protein is a key player linking inflammation and cancer. Due to the increased levels of calprotectin in different inflammatory diseases and cancer, it is considered as a marker for diagnostic purposes. In this study, we evaluated the mechanism of cell viability and apoptotic-inducing effects of recombinant human calprotectin (rhS100A8/S100A9) on the gastric adenocarcinoma (AGS), the most common type of gastric cancer cell line. AGS cells were exposed to the different concentrations (5–100 μg/ml) of calprotectin for 24, 48, and 72 h, and cell viability was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic-inducing effects of calprotectin were evaluated by sub-G1 cell cycle assay and Annexin V/propidium iodide double staining. Furthermore, real-time polymerase chain reaction and Western blot analysis were performed to evaluate the mechanism of action of calprotectin. Our findings indicated that calprotectin inhibits growth and viability of AGS cells in a time- and dose-dependent manner. The half-maximal inhibitory concentration values were measured as 85.77, 79.14, and 65.39 μg/ml for 24, 48, and 72 h, respectively. Additionally, we found that calprotectin downregulated the expression of antiapoptotic protein Bcl-2 and upregulated proapoptotic protein Bax in a time- and concentration-dependent fashion. Calprotectin also slightly upregulated the expression of extracellular signal-regulated protein kinase 2 (ERK2), while it significantly decreased the levels of phospho-ERK in a time-dependent manner. Overall, these findings indicated that calprotectin has cytotoxicity and apoptosis-inducing effects on AGS cell lines in high concentration by modulating Bax/Bcl-2 expression ratio accompanied by inhibition of ERK activation.

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Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells

World Journal of Gastroenterology ◽

10.3748/wjg.v22.i10.2971 ◽

2016 ◽

Vol 22 (10) ◽

pp. 2971 ◽

Cited By ~ 17

Author(s):

Kun Gao ◽

Qi Liang ◽

Zhi-Hao Zhao ◽

You-Fen Li ◽

Shu-Feng Wang

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Energy Metabolism ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Human Gastric Cancer ◽

Ags Cells ◽

Anticancer Properties ◽

Cycle Arrest

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An In Vitro Anti-Cancer Activity of Ocimum tenuiflorum Essential Oil by Inducing Apoptosis in Human Gastric Cancer Cell Line

Medicina ◽

10.3390/medicina57080784 ◽

2021 ◽

Vol 57 (8) ◽

pp. 784

Author(s):

Wongwarut Boonyanugomol ◽

Kamolchanok Rukseree ◽

Pornpan Prapatpong ◽

Onrapak Reamtong ◽

Seung-Chul Baik ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Migration And Invasion ◽

Human Gastric Cancer ◽

Ags Cells ◽

Anti Cancer ◽

Ocimum Tenuiflorum ◽

Cancer Activity

The effects of Ocimum tenuiflorum essential oil (OTEO) against gastric cancer remain unknown and merit investigation. In the present study, the anti-cancer activity of OTEO was examined in a human gastric cancer cell line (AGS). After OTEO treatment, AGS cell viability was determined by an MTT assay, and inhibition of metastasis was determined by cell migration and invasion assays. The expression of apoptosis-related genes in treated AGS cells was determined by qRT-PCR. OTEO significantly decreased AGS cell viability in a dose-dependent manner (IC50 163.42 µg/mL) and effectively inhibited cell migration and invasion. Morphological examination demonstrated that OTEO induced cell shrinkage, chromatin condensation, and fragmentation, which are considered typical morphologies of apoptotic cell death. Pro-apoptotic genes (TP53, BAX, and BAK) were significantly up-regulated, while anti-apoptotic genes (BCL-2 and BCL-xL) were significantly down-regulated after treatment with OTEO. In addition, significantly increased gene expression was detected for CASP8, CASP9, and CASP3 in AGS cells exposed to OTEO. GC-MS analysis demonstrated that the major compound of OTEO was caryophyllene (25.85%) and α-pinene (11.66%). This in vitro study demonstrates for the first time that OTEO has potential anti-gastric cancer activity and may induce apoptosis in AGS cells through extrinsic and intrinsic pathways.

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Inhibitory effect of endothelin A receptor blockade on tumor growth and liver metastasis of a human gastric cancer cell line

Gastric Cancer ◽

10.1007/s10120-007-0421-z ◽

2007 ◽

Vol 10 (2) ◽

pp. 123-128 ◽

Cited By ~ 8

Author(s):

Rika Fukui ◽

Hidefumi Nishimori ◽

Fumitake Hata ◽

Takahiro Yasoshima ◽

Keisuke Ohno ◽

...

Keyword(s):

Gastric Cancer ◽

Liver Metastasis ◽

Gastric Cancer Cell ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Inhibitory Effect ◽

Human Gastric Cancer ◽

Receptor Blockade ◽

Endothelin A Receptor ◽

Endothelin A

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Combined treatment with dissolved hydrogen molecule and platinum nanocolloid exerts carcinostatic/carcinocidal effects by increasing hydrogen peroxide generation and cell death in the human gastric cancer cell line NUGC-4

Free Radical Research ◽

10.1080/10715762.2021.1902514 ◽

2021 ◽

pp. 1-10

Author(s):

Yasukazu Saitoh ◽

Naho Kawasaki ◽

Natsumi Eguchi ◽

Minoru Ikeshima

Keyword(s):

Gastric Cancer ◽

Hydrogen Peroxide ◽

Hydrogen Molecule ◽

Gastric Cancer Cell ◽

Combined Treatment ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Human Gastric Cancer ◽

Dissolved Hydrogen ◽

Hydrogen Peroxide Generation

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Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803

Cellular & Molecular Biology Letters ◽

10.2478/s11658-006-0034-2 ◽

2006 ◽

Vol 11 (3) ◽

Cited By ~ 21

Author(s):

Hui Ling ◽

Liang-Yun Zhang ◽

Qi Su ◽

Ying Song ◽

Zhao-Yang Luo ◽

...

Keyword(s):

Gastric Cancer ◽

Specific Activity ◽

Lucifer Yellow ◽

Gastric Cancer Cell Line ◽

Major Constituent ◽

Diallyl Disulfide ◽

Human Gastric Cancer ◽

Dependent Manner ◽

Gastric Cancer Cells ◽

Induced Differentiation

AbstractDiallyl disulfide (DADS) is a major constituent of garlic. Previously, we found that DADS both inhibited proliferation in human gastric cancer cells in vitro and in vivo, and induced G2/M arrest. In this study, we investigated whether this differentiation effect was induced by DADS in human gastric cancer MGC803 cells, and whether it was related to an alteration in ERK activity. The results showed that the growth of MGC803 cells was inhibited by DADS. Cells treated with DADS displayed a lower nucleocytoplasmic ratio and tended to form gland and intercellular conjunction structures. The ConA-mediated cell agglutination ratio and cells’ ALP specific activity decreased. In MGC803 cells, dye transfer was limited to a few cells neighbouring the dye-injected cell and to a depth of 1–2 layers beneath the scrape site. However, after treatment with DADS, the LY (Lucifer Yellow) was transferred to several cells immediately neighbouring the microinjected cell and to a depth of 2–4 cell layers from the scrape site. This indicated that DADS induced differentiation in MGC803 cells. Western blot analysis revealed that although DADS did not influence the quantity of ERK1/2 protein expressed, it did decrease its phosphorylation in a concentration-dependent manner, compared with the controls. At 30 mg·L−1, DADS inhibited the activation of ERK1/2 in 15–30 min. These results suggested that the DADS-induced differentiation of MGC803 cells involved an alteration of the ERK1/2 signaling pathway.

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