• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.370-379
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• 2020

Econazole, a potent broad-spectrum antifungal agent and a Ca²⁺ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.10
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• pp.1500-1509
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• 2014

The object of this study was to investigate the inhibitory effects of chios mastic gum (MG) on gastric acid secretion in an ethanol-induced SD rat model and primary parietal cells. Rats were randomly divided into four groups: Vehicle (normal group), Control (treated with ethanol), MG50 (treated with ethanol and mastic gum at 50 mg/kg b.w), MG100 (treated with ethanol and mastic gum at 100 mg/kg b.w). Groups treated with both MG50 and MG100 showed attenuation of gastric mucosal injury, sub-epithelial loss, hemorrhaging, and gastric juice secretion. We also examined the acidity of gastric juice during gastric injury. Oral administration of both MG50 and MG100 significantly decreased acidity of gastric juice by % and %, respectively. To examine the stimulatory factors related to gastric acid secretion, mRNA expression levels of H2r, M3r, CCK2r, and $H^+/K^+$ ATPase were measured by real-time PCR. Compared with a vehicle group, mRNA expression levels of H2r, CCK2r, and $H^+/K^+$ ATPase clearly increased in the control group. However, levels of H2r, CCK2r, and $H^+/K^+$ ATPase slightly but significantly decreased in MG-treated groups compared with control. Blood level of histamine significantly decreased in MG-treated groups, which indicates the involvement of MG on in histamine-related acid secretion. To identify the mode of action of MG in regulating histamine-related pathways, intracellular level of cAMP and mRNA levels of H2r, M3r, CCK2r, and $H^+/K^+$ ATPase were measured in primary parietal cells. While mRNA levels of M3r and CCK2r remained unchanged, levels of H2r and $H^+/K^+$ ATPase significantly decreased upon MG treatment. Subsequently, intracellular levels of cAMP decreased. These results suggest that mastic gum has the ability to inhibit gastric acid secretion by regulating a histamine-related pathway.

• Korean Journal of Pharmacognosy
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• v.36 no.1 s.140
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• pp.38-43
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• 2005

This study was undertaken to evaluate the gastrotherapeutic effects of the extract of Rosa rugosa. It can be regarded that the antigastric and anti-ulcerative effect of Rosa rugosa is originated from the reduction of total acid output identified by gastric secretion test. To clarify the protective mechanism of the Rosa rugosa extract, the gastropathy was induced in rats with alcohol-salicylate and the activities of the free radical scavenging enzymes were examined. The acitivity of superoxide dismutase and glutathione peroxide were significantly increased and the total content of glutathione was recovered. We concluded that the protective effect of the extract of Rosa rugosa on gastropathy in rats is its ability increased the activities of the free radical scavenging enzymes.

• Food Science and Preservation
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• v.24 no.7
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• pp.1017-1024
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• 2017

The objective of this study was to investigate the inhibitory effects of Litsea japonica fruit flesh extract (LJF-HE) on gastritis in an indomethacin-induced SD rat model. Rats were randomly divided into six groups: G1 (normal group), G2 (control group, indomethacin-induced gastritis), G3 (positive group, indomethacin-induced gastritis and ranitidine 50 mg/kg), G4 (LJF-HE-L group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 30 mg/kg), G5 (LJF-HE-M group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 60 mg/kg), G6 (LJF-HE-H group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 120 mg/kg). In the group treated with LJF-HE (G4, G5, and G6), gastric mucosal damage, gastric juice secretion and pepsin activity were significantly decreased compared to the control group. Additionally, there were decreases in the expression of cholecystokinin 2 receptor (CCK-2r), histamine receptor H2 (H2r) and H+/K+ ATPase in the gastric lesions. The plasma levels of TNF-${\alpha}$ and IL-$1{\beta}$ significantly decreased in LJF-HE (G4, G5, and G6) treated groups compared with control. The plasma level of PGE2 was also significantly increased by LJF-HE (G5 and G6). These results suggest that LJF-HE (G4, G5, and G6) has the ability to inhibit on indomethacin-induced gastritis.

• Applied Microscopy
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• v.41 no.1
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• pp.1-11
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• 2011

This experiment was performed to evaluate the morphological responses of the gastric epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of 5-fluorouracil, mitomycin C or Acriflavine-Guanosine compound (AG60). In this study, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline, 5-fluorouracil (30 mg/kg), mitomycin C ($400{\mu}g/kg$) or AG60 (30 mg/kg) were injected to the animals every other day, respectively. Each animals were sacrificed after 7th injection and tissue were taken from the gastric mucosa. Thereafter, the ultrathin sections were stained with uranyl acetate and lead citrate. In the 5-fluorouracil-, mitomycin C- or AG60-treated mice, myelin figures and multivesicular bodies within the gastric mucous epithelial cells were observed more frequently than those of the normal control. In the 5-fluorouracil-treated mice, membrane structures containing a few mucous granules in the luminal space were observed. Indeed, bulging cytoplasmic process containing mucous granules protruding into the gastric lumen were observed in the mitomycin Ctreated mice. Therefore, this study suggested that AG60 as compared with 5-fluorourail and mitomycin C may effective medicine without damage to the secretion ability of gastric mucous epithelial cells.

• Journal of Life Science
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• v.14 no.6 s.67
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• pp.906-912
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• 2004

Helicobacter pylori infection is highly prevalent, as high as 2/3 of whole population infected, in Korea. H. pylori infection initiates inflammation by induction of interleukin-8 through type IV secretion of CagA. It was recently suggested that induction failure of IL-8 is not associated with defect in cag PAI but associated with cagE locus diversity. This study was designed to investigate ability of 11-8 in-duction according to sequence variation within the cagE gene, cagA TP motifs and vacA m-types in vitro study using AGS cell-line, and to evaluate its association with different clinical outcome. Seventy-four H. pylori stains were isolated from 23 patients with gastric cancer (Ca), 24 subjects with gastritis (G) and 27 patients with duodenal ulcer (Du) in Kangnam St. Mary's Hospital, Seoul, Korea. cagE gene diversity was confirmed by the PCR-RFLP methods with MboI/NlaIII and tyrosine phosphate motifs (TPMs) of cagA was determined TPM-A and C by using DdeI/Tsp5091 restriction enzyme and TPM-B was determend by Real time PCR the method of Owen et al. and IL-8 was measured by ELISA assay. IL-8 activity was positively detected in 59 among 74 strains $(79.7\%)$. IL-8 secretion was significantly increased in MboI A and MboI B type compared to MboI C type and in MboI/NlaIII A-C and B-C type than C-C type. 1L-8 activity was not associated with either the number or composition of cagA tyrosine phosphorylation motifs and vacA m-type. There was no significant difference in IL-8 activity among patient groups. cagE gene diversity is thought to be mainly associated with the induction of IL-8 in H. pylori infection.