Improvement of the Chemosensitivity of Gastric Carcinoma Cells by Celastrus orbiculatus Extracts

Gastric carcinoma is one of the most prevalent malignancies with high morbidity and mortality. While chemotherapy is the major means for the management gastric carcinoma, tumors gradually exhibit drug resistance. Therefore, there is a need for agents capable of enhancing the sensitivity of tumor cells to chemotherapy. Herein, we have examined the effect of Celastrus orbiculatus extracts on chemosensitivity of drug resistant gastric carcinoma cells. Human gastric carcinoma cells (MGC-803 and SGC-7901) were cultured in the presence of cisplatin for the selection of drug resistant gastric cells. Next, the effect of C. orbiculatus extracts on multiplication capacity of drug resistant MGC-803 and SGC-7901 cells was examined by a variety of measures. Following C. orbiculatus extract treatment, the multiplication and invasiveness of drug resistant MGC-803 and SGC-7901 cells declined remarkably, with increased apoptosis and decreased levels of β-catenin, c-Myc, and cyclin D1 proteins, protein markers critical to cell proliferation, differentiation, and apoptosis. In summary, C. orbiculatus extract can effectively improve the sensitivity of cisplatin resistant gastric carcinoma cells to cisplatin and promote the apoptosis of tumor cells through the inhibition of the expression of proteins associated with the Wnt/β-catenin axis.

Chitosan Inhibits Helicobacter pylori Growth and Urease Production and Prevents Its Infection of Human Gastric Carcinoma Cells

This study investigated the effects of shrimp chitosan with 95% degree of deacetylation (DD95) in combination with clinical antibiotics on the growth and urease production of Helicobacter pylori. The inhibitory effect of DD95 on the adherence of H. pylori to the human intestinal carcinoma cells (TSGH9201) was also investigated. Five strains of H. pylori, including three standard strains and two strains of clinical isolates were used as the test strains. The inhibitory effects of DD95 on growth and urease production of various strains of H. pylori increased with increasing DD95 concentration and decreasing pH values from pH 6.0 to pH 2.0. Urease activity of H. pylori at pH 2.0 in the presence of 4000 μg/mL of DD95 decreased by 37.86% to 46.53%. In the presence of 50 μg/mL antibiotics of amoxicillin, tetracycline, or metronidazole at pH 6.0 and pH 2.0, H. pylori counts were decreased by 1.51–3.19, and 1.47–2.82 Log CFU/mL, respectively. Following the addition of 4000 μg/mL DD95 into the 50 μg/mL antibiotic-containing culture medium with pH 6.0 and pH 2.0, overall H. pylori counts were strongly decreased by 3.67–7.61 and 6.61–6.70 Log CFU/mL, respectively. Further, DD95 could inhibit the adherence of H. pylori on TSGH 9201 cells, as evidenced by fluorescent microscopy and thus may potentially protect against H. pylori infection.

Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells

Gastric cancer (GC) is the most common cancer throughout the world. Despite advances of the treatments, detailed oncogenic mechanisms are largely unknown. In our previous study, we investigated microRNA (miR) expression profiles in human GC using miR microarrays. We found miR-192/215 were upregulated in GC tissues. Then gene microarray was implemented to discover the targets of miR-192/215. We compared the expression profile of BGC823 cells transfected with miR-192/215 inhibitors, and HFE145 cells transfected with miR-192/-215 mimics, respectively. SET8 was identified as a proposed target based on the expression change of more than twofold. SET8 belongs to the SET domain-containing methyltransferase family and specifically catalyzes monomethylation of H4K20me. It is involved in diverse functions in tumorigenesis and metastasis. Therefore, we focused on the contributions of miR-192/215/SET8 axis to the development of GC. In this study, we observe that functionally, SET8 regulated by miR-192/215 is involved in GC-related biological activities. SET8 is also found to trigger oncogene-induced senescence (OIS) in GC in vivo and in vitro, which is dependent on the DDR (DNA damage response) and p53. Our findings reveal that SET8 functions as a negative regulator of metastasis via the OIS-signaling pathway. Taken together, we investigated the functional significance, molecular mechanisms, and clinical impact of miR-192/215/SET8/p53 in GC.

Potentially Bioaccessible Phenolics from Mung Bean and Adzuki Bean Sprouts Enriched with Probiotic—Antioxidant Properties and Effect on the Motility and Survival of AGS Human Gastric Carcinoma Cells

Gastric digests from mung (MBS) and adzuki (ABS) bean sprouts enriched with probiotic Lactobacillus plantarum 299v were tested for their antioxidant potential, as well as antiproliferative and antimotility properties, in human stomach cancer cells (AGS). The digest of ABS contained quercetin and kaempferol derivates, while kaempferol and apigenin derivates were dominant in MBS. Compared to the controls, the probiotic-rich sprouts had a higher antioxidant potential—by 13% and 9%, respectively. Adzuki bean sprouts decreased the viability of AGS already at low concentrations (25% motility inhibitions). MBS and ABS displayed dose-independent cytostatic effects. The ABS extracts decreased the proliferation of AGS more effectively than the MBS extracts—0.2‰ ABS exerted c.a. 70% of inhibitions. Moreover, the phytochemicals from the probiotic-rich sprouts considerably reduced this activity. The increased vinculin level, the apoptotic shape of cell nuclei, and the reduced cell motility and proliferation indicate that the extracts exhibited cytostatic and cytotoxic activity.