Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myeloid cell leukemia-1 (Mcl-1, Mcl-1L) is an anti-apoptotic protein of the Bcl-2 family that acts as a critical molecule in apoptosis control. Mcl-1 pre-mRNA can undergo alternative splicing to yield the short isoform, Mcl-1S, which resembles BH3-only pro-apoptotic proteins and induces apoptosis. Overexpression of Mcl-1 may play a role in various human tumors, and Mcl-1 may serve as a target in cancer therapy. In this study, we found an imbalance between the expression levels of Mcl-1L and Mcl-1S in the skin basal cell carcinoma (BCC) cell line when compared with primary keratinocytes. We showed that overexpression of Mcl-1S induces apoptosis in BCC cells. Finally, we showed that Mcl-1 antisense morpholino oligonucleotides (AMOs) can specifically target Mcl-1 pre-mRNA and shift the splicing pattern from Mcl-1L to Mcl-1S mRNA and protein. This shift increases the level of pro-apoptotic Mcl-1S and reduces the level of anti-apoptotic Mcl-1L, which induces apoptosis in BCC cells and AGS cells, a human gastric adenocarcinoma epithelial cell line. Thus, this report provides a strategy for cancer therapy in which AMOs change the alternative splicing pattern of Mcl-1 pre-mRNA and thereby induce apoptosis.
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PMID:Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells. 1936 67

The antiproliferative activity of the diterpenes jatropholone A and B, 16 semi-synthetic derivatives thereof, and that of jatrophone and its three derivatives was assessed on human cell cultures. The cells used comprised normal lung fibroblasts (MRC-5), gastric adenocarcinoma (AGS), leukemia (HL-60), lung cancer (SK-MES-1), and bladder carcinoma (J82). Jatropholone A ( 1) was inactive against all the tumor cell lines; however, its acetylation rendered a compound with antiproliferative activity. The epimeric jatropholone B ( 8) was active against all the cancer cell lines, and its derivatives presented different effects on the selected cell lines. While jatrophone ( 19) showed strong anticancer activity, its derivatives 9beta,13alpha-dihydroxyisabellione and 13alpha-hydroxy-9 beta-acetoxyisabellione were less active.
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PMID:Antiproliferative activity of the diterpenes jatrophone and jatropholone and their derivatives. 1956 59

Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis has been reported in some cancer cells, including AGS human gastric adenocarcinoma cells. Hizikia fusiforme is a commonly used brown seaweed species in Korea that possesses potent antibacterial, antifungal, and anti-inflammatory activities. In this study, we demonstrated that treatment with TRAIL in combination with subtoxic concentrations of ethyl alcohol extract of H. fusiforme (EAHF) sensitized TRAIL-resistant AGS cells to TRAIL-mediated apoptosis. Combined treatment with EAHF and TRAIL increased chromatin condensation, DNA fragmentation, and sub-G1-phase DNA content. The restored sensitivity to TRAIL-induced apoptosis appeared to be correlated with the modulation of Bcl-2 family proteins and activation of caspases, which resulted in the cleavage of poly(ADP-ribose)polymerase. Taken together, the use of EAHF in combination with TRAIL may be an effective and selective anticancer strategy via suppressing the resistance to TRAIL-induced apoptosis in some tumor cell lines, including AGS cells.
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PMID:Ethyl alcohol extracts of Hizikia fusiforme sensitize AGS human gastric adenocarcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis. 1973 77

A screening study using a luciferase assay to identify natural products that enhance death receptor 5 (DR5) expression was carried out, and bioassay-guided fractionation of two organisms, the pericarp of Garcinia mangostana (mangosteen) and actinomycete CKK609 strain, led to the isolation of eight xanthone derivatives (1-8) and teleocidin A-2 (9). Among them, compounds 1, 2, and 5, isolated from G. mangostana, and 9, from the actinomycete, showed potent DR5 promoter activity. Furthermore, we revealed that combined treatment with gartanin (5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) showed a potentiation effect in sensitizing TRAIL-resistant human gastric adenocarcinoma (AGS) cells. Thus, the present results suggested that 5 has the ability to overcome TRAIL resistance via the up-regulation of DR5 and may be an effective sensitizer of TRAIL-resistant cells.
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PMID:Activity of mangosteen xanthones and teleocidin a-2 in death receptor expression enhancement and tumor necrosis factor related apoptosis-inducing ligand assays. 1978 89

The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1-suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.
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PMID:MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2. 1984 62

Prostaglandin (PG) E(2) promotes gastrointestinal carcinogenesis and tumor progression. We determined the correlations between pattern of expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a catabolic enzyme for biological inactivation of PGE(2), in gastric adenocarcinoma and various clinicopathological factors and patient outcome in an attempt to elucidate its biological significance. In 35 of 71 cases of gastric adenocarcinoma, expression of 15-PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15-PGDH expression to be an independent predictor of poor survival. The proportion of Ki67-positive cells in 15-PGDH-negative adenocarcinoma was higher than that in 15-PGDH-positive adenocarcinoma. No differences were found in clinicopathological parameters between patients with cyclooxygenase-2 (COX-2)-positive tumors and those with COX-2 negative tumors. In an in vitro study, use of specific siRNA to silence 15-PGDH or a specific inhibitor of 15-PGDH enhanced cell proliferation in the gastric cancer cell line AGS, which expresses 15-PGDH. These findings suggest that reduction of 15-PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma.
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PMID:Reduction of 15-hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma. 1991 58

Previously, we have reported tissue- and stage-specific expression of miR-372 in human embryonic stem cells and so far, not many reports speculate the function of this microRNA (miRNA). In this study, we screened various human cancer cell lines including gastric cancer cell lines and found first time that miR-372 is expressed only in AGS human gastric adenocarcinoma cell line. Inhibition of miR-372 using antisense miR-372 oligonucleotide (AS-miR-372) suppressed proliferation, arrested the cell cycle at G2/M phase, and increased apoptosis of AGS cells. Furthermore, AS-miR-372 treatment increased expression of LATS2, while over-expression of miR-372 decreased luciferase reporter activity driven by the 3' untranslated region (3' UTR) of LATS2 mRNA. Over-expression of LATS2 induced changes in AGS cells similar to those in AGS cells treated with AS-miR-372. Taken together, these findings demonstrate an oncogenic role for miR-372 in controlling cell growth, cell cycle, and apoptosis through down-regulation of a tumor suppressor gene, LATS2.
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PMID:miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2. 1993 37

Sanguinarine is a benzophenanthridine alkaloid, derived from the root of Sanguinaria canadensis and other poppy Fumaria species, which is known to have antimicrobial, antiinflammatory and antioxidant properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells but spare most normal cells. However, its effects are limited in some types of cancer cells, including AGS human gastric adenocarcinoma cells. In the present study, we showed that treatment with TRAIL in combination with subtoxic concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in AGS cells. Combined treatment with sanguinarine and TRAIL effectively induced Bid cleavage and loss of mitochondrial membrane potential, leading to the activation of caspases, and cleavage of poly(ADP-ribose) polymerase and beta-catenin. The cytotoxic effects of the combined treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase-3 in the observed cytotoxic effect. In addition, the levels of Akt protein were markedly reduced in cells co-treated with sanguinarine and TRAIL. Apoptosis induced by the combined treatment was markedly increased by the phosphatidylinositol-3'-kinase inhibitor, LY294002 (Akt-upstream inhibitor), through the mitochondrial amplification step and caspase activation, suggesting that interactions of the synergistic effect were at least partially mediated through the Akt-dependent pathway.
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PMID:Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated apoptosis via down-regulation of AKT and activation of caspase-3. 2003 92

Anticancer effects of chungkukjang (a Korean short-term fermented soy paste) were studied in human gastric adenocarcinoma cells, and Bacillus strains from chungkukjang were isolated and identified. Before the experiments, six different chungkukjang products (K-, M-, Mn-, O-, Os-, and H-chungkukjangs) were purchased from a folk village in the Sunchang region, Jeonbuk, Republic of Korea. Based on sensory evaluation tests and general chemical and quality studies, K-, H-, and M-chungkukjangs were selected for the experiments. All chungkukjang samples exhibited in vitro anticancer activities; however, K-chungkukjang revealed the highest anticancer activity in the previous studies. In this experiment, K-chungkukjang again showed the highest anticancer effect in the AGS cells. At the concentration of 1 mg/mL, K-chungkukjang (87%) showed the highest growth inhibitory effect, followed by H-chungkukjang (85%) and MC-chungkukjang (69%) (P < .05). K-chungkukjang induced apoptosis as determined by 4,6-diamidino-2-phenylindole staining and exhibited increased bax and decreased bcl-2 mRNA expression. Three representative Bacillus strains from K-chungkukjang were isolated and identified by recA gene sequencing as Bacillus cereus, Bacillus amyloliquefaciens, and Bacillus subtilis. Identifying B. cereus in the chungkukjang means that when chungkukjang is prepared by the traditional method, B. cereus, which is a common cause of foodborne disease, can grow during the natural fermentation process. All B. cereus strains, of course, are not pathogens, but its presence causes food safety concerns. Therefore, using a starter culture is safer than the traditional natural fermentation for the industrialization of chungkukjang in Korea.
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PMID:Identification of Bacillus cereus in a chungkukjang that showed high anticancer effects against AGS human gastric adenocarcinoma cells. 2004 81

The aims of this work were to compare antiproliferation, antioxidant activities and total phytochemicals and individual isoflavone profiles in soy milk processed by various methods including traditional stove cooking, direct steam injection, direct ultrahigh temperature (UHT), indirect UHT, and a two-stage simulated industry method, and a selected commercial soy milk product. Various processing methods significantly affected total saponin, phytic acid, and total phenolic content and individual isoflavone distribution. The laboratory UHT and the two-stage processed soy milk exhibited relatively higher total phenolic content, total flavonoid content, saponin and phytic acid than those processed by the traditional and steam processed methods. Thermal processing caused obvious intertransformation but did not cause severe degradation except for breaking down of aglycons. Thermal processing significantly increased antioxidant capacities of soy milk determined by chemical analyses, but decreased cellular antioxidant capacities as compared to the raw soy milk. The raw and all processed soy milk exhibited antipoliferative activities against human HL-60 leukemia cells, AGS gastric tumor cells, and DU145 prostate cancer cells in a dose-dependent manner. The raw soy milk, but not the processed soy milk, exhibited a dose-dependent antiproliferative effect against colorectal adenocarcinoma Caco-2 cells. Taken together, these results indicate that various thermal processing methods change not only phytochemcials but also potential health-promoting effects of soy milk.
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PMID:Comparative studies on the chemical and cell-based antioxidant activities and antitumor cell proliferation properties of soy milk manufactured by conventional and commercial UHT methods. 2015 54


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