18ß-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling.

18ß-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of cancer. In the present study, we found that GRA attenuated the severity of gastritis and suppressed gastric tumorigenesis in transgenic mice. We also discovered that miR-149-3p was downregulated in gastric cancer tissues and cell lines as compared to normal gastric tissues and epithelial cells, but was upregulated by GRA. miR-149-3p expression also correlated negatively with lymphnode metastasis. Our functional assays showed that miR-149-3p overexpression inhibited cell proliferation and cell cycle progression while inducing apoptosis, while inhibition of miR-149-3p had the opposite effects. In addition, we identified Wnt-1 as a direct target of miR-149-3p. These data suggest that GRA inhibits the initiation and progression of gastric tumors by ameliorating the inflammatory microenvironment through downregulation of COX-2 expression and by inhibiting Wnt-1 expression through the upregulation of tumor suppressor miR-149-3p. GRA may thus have the potential to serve as a useful therapeutic agent for the prevention and treatment of gastric cancer.

The Protective Effects of 18ß-Glycyrrhetinic Acid on Helicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils.

18ß-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1ß, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower (2.14 ± 0.08 versus 3.17 ± 0.23, P < 0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P < 0.05), and the expression levels of TNF-α, IL-1ß, COX-2, and iNOS were decreased (P < 0.05) compared with the H. pylori-infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug.

Matrine inhibited proliferation and increased apoptosis in human breast cancer MCF-7 cells via upregulation of Bax and downregulation of Bcl-2.

PURPOSE: The aim of the present study was to investigate the effects of matrine on proliferation and apoptosis in human breast cancer MCF-7 cells and its relevant molecular mechanisms. METHODS: Breast carcinoma cell line MCF-7 was cultured with series concentrations of Matrine in vitro. The proliferation and apoptosis of MCF-7 cells were investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Mitochondrial membrane potential (MMP) measurements. The expression levels of Bax and Bcl-2 proteins were detected by Annexin V/propidium iodide coupled staining. The morphological changes of MCF-7 cell were examined. RESULTS: The inhibition rates of MCF-7 cells were 6.01%-37.01%, 7.56%-53.92%, and 10.86%-70.23% for 24, 48, and 72 hours after Matrine treatment, respectively. The proliferation of MCF-7 cells was significantly inhibited by Matrine administration, with a time and dose dependent manner. The rates apoptotic cells was between 4.17±0.25% and 19.63±0.17% in 0.25-2.0 mg/ml Matrine groups, which had significant increased compare with the control groups (1.10±0.08%, P<0.05). Meanwhile, increased Bax expression, but decreased Bcl-2 expression was observed in MCF-7 cell line. MMP were significantly decreased by Matrine treatment. CONCLUSIONS: Matrine significantly inhibited the growth and induced apoptosis in breast carcinoma MCF-7 cells, which is related to Bax, Bcl-2 signaling and MMP.