lignans and Stomach-Neoplasms

lignans has been researched along with Stomach-Neoplasms* in 24 studies

Reviews

2 review(s) available for lignans and Stomach-Neoplasms

ArticleYear
Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.
    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2015, Volume: 18, Issue:3

    The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk.. Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated.. In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction < 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction < 0.01).. Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

    Topics: 4-Butyrolactone; Adenosylmethionine Decarboxylase; Asian People; Case-Control Studies; Equol; Gene-Environment Interaction; Genistein; Humans; Isoflavones; Lignans; Multicenter Studies as Topic; NAD(P)H Dehydrogenase (Quinone); Nitric Oxide Synthase Type II; Ornithine Decarboxylase; Phytoestrogens; Polyamines; Polymorphism, Single Nucleotide; Stomach Neoplasms

2015
[The role of integrin in the invasion and metastasis of gastric cancer].
    Nihon rinsho. Japanese journal of clinical medicine, 2001, Volume: 59 Suppl 4

    Topics: Cell Adhesion; Extracellular Matrix; Humans; Integrins; Lignans; Neoplasm Invasiveness; Neoplasm Metastasis; Signal Transduction; Stomach Neoplasms

2001

Other Studies

22 other study(ies) available for lignans and Stomach-Neoplasms

ArticleYear
Schisandrin B suppresses gastric cancer cell growth and enhances the efficacy of chemotherapy drug 5-FU in vitro and in vivo.
    European journal of pharmacology, 2022, Apr-05, Volume: 920

    Gastric cancer (GC) is a serious affliction worldwide and remains to be the fourth most common cancer with poor prognosis, especially in advanced stage. Chemotherapy is one of the main therapeutic means. The purpose of this study was to investigate the antitumor effects of Schisandrin B (Sch B) on GC cells both in vitro and in vivo, as well as the synergistic effect with 5-fluorouracil (5-FU), and to preliminarily explore the relevant mechanism of action. Our results showed that Sch B inhibited the growth, migration and invasion of GC cells. Besides, Sch B could effectively inhibit the phosphorylation of STAT3 (signal transducer and activator of transcription 3), induce autophagy, and enhance the efficacy of chemotherapy drug 5-FU in vitro and in vivo. Taken together, the findings indicate that Sch B displays potent antitumor activities. The co-administration of Sch B and 5-FU might be a promising way for future therapy of GC.

    Topics: Apoptosis; Cell Line, Tumor; Cyclooctanes; Fluorouracil; Humans; Lignans; Polycyclic Compounds; Stomach Neoplasms

2022
Schizandrin A induces the apoptosis and suppresses the proliferation, invasion and migration of gastric cancer cells by activating endoplasmic reticulum stress.
    Molecular medicine reports, 2021, Volume: 24, Issue:5

    Apart from its basic antioxidant and anti‑inflammatory properties, schizandrin A (SchA), which is isolated from

    Topics: Apoptosis; Cell Cycle; Cell Movement; Cell Proliferation; Cyclooctanes; Endoplasmic Reticulum Stress; Humans; Lignans; Neoplasm Invasiveness; Polycyclic Compounds; Stomach Neoplasms; Tumor Cells, Cultured; Wound Healing

2021
Functional vinorelbine plus schisandrin B liposomes destroying tumor metastasis in treatment of gastric cancer.
    Drug development and industrial pharmacy, 2021, Volume: 47, Issue:1

    Gastric cancer is one of the leading causes of cancer-related death worldwide with a poor prognosis. Gastric cancer is usually treated with surgery and chemotherapy, accompanied by a high rate of metastasis and recurrence. In this paper, R

    Topics: Animals; Apoptosis; Cell Line, Tumor; Cyclooctanes; Lignans; Liposomes; Mice; Mice, Nude; Polycyclic Compounds; Stomach Neoplasms; Vinorelbine

2021
Schisantherin A induces cell apoptosis through ROS/JNK signaling pathway in human gastric cancer cells.
    Biochemical pharmacology, 2020, Volume: 173

    Gastric cancer is one of the most lethal cancers with unmet clinical treatment and low 5-year survival rate. Schisantherin A is a major compound derived from Fructusschisandrae while its anti-tumor role remains nearly unknown. Here, we reported that schisantherin A had an anti-proliferation effect on gastric cancer cell lines MKN45 and SGC-7901. Schisantherin A induced cell cycle arrest at G2/M phase and cell apoptosis, and inhibited cell migration in gastric cancer MKN45 and SGC7901 cells. Meanwhile, upregulation of cleaved caspase-9, cleaved caspase-3 and cleaved PARP were accompanied with the loss of mitochondrial membrane potential (MMP). Moreover, schisantherin A induced ROS-dependent JNK phosphorylation with higher ROS production. The JNK inhibitor and ROS scavenger NAC rescued the cell apoptosis and cycle inhibition elicited by schisantherin A. Furthermore, the expression level of antioxidant factor Nrf2 was suppressed by schisantherin A. These findings suggest that schisantherin A possesses an anti-tumor activity via activation of ROS/JNK with Nrf2 inhibition, indicating that schisantherin A is a promising chemotherapeutic candidate for gastric cancer.

    Topics: Apoptosis; Caspases; Cell Line, Tumor; Cell Movement; Cyclooctanes; Dioxoles; G2 Phase Cell Cycle Checkpoints; Humans; Lignans; MAP Kinase Signaling System; Membrane Potential, Mitochondrial; Molecular Structure; Phosphorylation; Plant Extracts; Reactive Oxygen Species; Schisandra; Stomach Neoplasms

2020
Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism.
    Medical science monitor : international medical journal of experimental and clinical research, 2020, Aug-30, Volume: 26

    BACKGROUND The purpose of our study was to determine the effects and mechanisms of honokiol on human epidermal growth factor receptor 2 (HER2)-positive gastric cancer cells by in vitro study. MATERIAL AND METHODS We measured HER2 expression in different gastric cancer cell lines by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) assay. Cell proliferation, apoptosis, and cell cycle were evaluated by cell-counting kit 8 and flow cytometry assays. The invading cell numbers and wound-healing rates were measured by transwell and wound-healing assays. Phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), P21, and matrix metalloproteinase (MMP)-9 proteins and messenger ribonucleic acid (mRNA) expression were measured by WB and RT-qPCR assay. HER2 protein expression was evaluated by cellular immunofluorescence. RESULTS Honokiol suppressed cell proliferation via increasing cell apoptosis, invasion, and migration with dose dependence. By WB and RT-qPCR assays, compared with the control group, PI3K, AKT, P21, and MMP-9 proteins and mRNA expression were significantly different (P<0.05). By cellular immunofluorescence, HER2 protein expression was significantly depressed in honokiol-treated groups compared with control groups (P<0.05). CONCLUSIONS Honokiol has suppressive effects on HER2-positive gastric cancer cell biological activities via regulation of HER2/PI3K/AKT pathways in vitro.

    Topics: Apoptosis; Biphenyl Compounds; Case-Control Studies; Cell Proliferation; Humans; Lignans; Matrix Metalloproteinase 9; Phosphatidylinositol 3-Kinase; Receptor, ErbB-2; RNA, Messenger; Stomach Neoplasms; Tumor Cells, Cultured

2020
Two new lignans from twigs of Aglaia odorata.
    Journal of Asian natural products research, 2016, Volume: 18, Issue:2

    HPLC-guided separation of twigs of Aglaia odorata led to the isolation of eight lignans, including two new ones, 3'-methoxy-N-demethylrocaglamide (1) and 4'-O-demethyl-deacetylaglaxiflorin A (2). Compound 1 showed excellent cytotoxicity against three human cancer cell lines, HeLa, SGC-7901 gastric cancer, and A-549 lung cancer with the values of 0.32, 0.12, and 0.25 μM, respectively.

    Topics: Aglaia; Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; HeLa Cells; Humans; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Stems; Stomach Neoplasms

2016
Antitumor lignanamides from the aerial parts of Corydalis saxicola.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2016, Dec-01, Volume: 23, Issue:13

    Cancer is one of the leading cause of unnatural death globally. There is still a great need for effective anticancer agents from plant sources. Corydalis saxicola Bunting is a medicinal plant that is traditionally used to treat various diseases in southwest China. Previous phytochemical investigations of C. saxicola have focused on isoquinoline alkaloids that have been isolated, which have activity against anti-hepatitis B virus and inhibit DNA topoisomerase I. However, the exploration of other classes of constituents and their bioactivities needs further study.. The aim of this study was to investigate the antitumor activity of isolated lignanamides as well as their detailed cellular proliferation, suppression, and cytotoxic mechanisms.. Herbs were extracted and constituents were purified by chromatographic separation, including silica gel, ODS, MCI, Sephadex LH-20 and Preparative HPLC. The compound structures were elucidated by the use of UV, IR, NMR and MS spectral data. The cytotoxicity effects of all compounds from the MGC-803, HepG2, T24, NCI-H460, Spca-2, and HL-7702 cell lines were studied by MTT assays. The induction of apoptosis by corydalisin C was investigated using acridine orange/ethidium bromide staining, Hoechst 33,258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry.. Three new lignanamides, together with five known analogues, were isolated from the aerial parts of C. saxicola. Corydalisin C possessed the most potent inhibitory effects, with an IC. This study provides evidence that a lignanamide from the ethyl acetate extract of whole plants of C. saxicola showing potential in cancer treatment.

    Topics: Amides; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Proliferation; China; Chromatography, High Pressure Liquid; Corydalis; Drug Screening Assays, Antitumor; Humans; Lignans; Membrane Potential, Mitochondrial; Plant Components, Aerial; Plants, Medicinal; Stomach Neoplasms; Structure-Activity Relationship

2016
Honokiol confers immunogenicity by dictating calreticulin exposure, activating ER stress and inhibiting epithelial-to-mesenchymal transition.
    Molecular oncology, 2015, Volume: 9, Issue:4

    Peritoneal dissemination is a major clinical obstacle in gastrointestinal cancer therapy, and it accounts for the majority of cancer-related mortality. Calreticulin (CRT) is over-expressed in gastric tumors and has been linked to poor prognosis. In this study, immunohistochemistry studies revealed that the up-regulation of CRT was associated with lymph node and distant metastasis in patients with gastric cancer specimens. CRT was significantly down-regulated in highly metastatic gastric cancer cell lines and metastatic animal by Honokiol-treated. Small RNA interference blocking CRT by siRNA-CRT was translocated to the cells in the early immunogenic response to Honokiol. Honokiol activated endoplasmic reticulum (ER) stress and down-regulated peroxisome proliferator-activated receptor-γ (PPARγ) activity resulting in PPARγ and CRT degradation through calpain-II activity, which could be reversed by siRNA-calpain-II. The Calpain-II/PPARγ/CRT axis and interaction evoked by Honokiol could be blocked by gene silencing or pharmacological agents. Both transforming growth factor (TGF)-β1 and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced cell migration, invasion and reciprocal down-regulation of epithelial marker E-cadherin, which could be abrogated by siRNA-CRT. Moreover, Honokiol significantly suppressed MNNG-induced gastrointestinal tumor growth and over-expression of CRT in mice. Knockdown CRT in gastric cancer cells was found to effectively reduce growth ability and metastasis in vivo. The present study provides insight into the specific biological behavior of CRT in epithelial-to-mesenchymal transition (EMT) and metastasis. Taken together, our results suggest that the therapeutic inhibition of CRT by Honokiol suppresses both gastric tumor growth and peritoneal dissemination by dictating early translocation of CRT in immunogenic cell death, activating ER stress, and blocking EMT.

    Topics: Adult; Animals; Biomarkers, Tumor; Biphenyl Compounds; Calpain; Calreticulin; Cell Death; Cell Line, Tumor; Down-Regulation; Endoplasmic Reticulum Stress; Epithelial-Mesenchymal Transition; Female; Gene Knockdown Techniques; Humans; Lignans; Macrophages; Male; Methylnitronitrosoguanidine; Mice, Inbred BALB C; Mice, Inbred C57BL; Middle Aged; Neoplasm Invasiveness; Phagocytosis; PPAR gamma; Promoter Regions, Genetic; Protein Binding; Stomach Neoplasms; Up-Regulation

2015
Honokiol thwarts gastric tumor growth and peritoneal dissemination by inhibiting Tpl2 in an orthotopic model.
    Carcinogenesis, 2013, Volume: 34, Issue:11

    Honokiol is known to suppress the growth of cancer cells; however, to date, its antiperitoneal dissemination effects have not been studied in an orthotopic mouse model. In the present study, we evaluated the antiperitoneal dissemination potential of Honokiol in an orthotopic mouse model and assessed associations with tumor growth factor-β1 (TGFβ1) and cells stimulated by a carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Our results demonstrate that tumor growth, peritoneal dissemination and peritoneum or organ metastasis of orthotopically implanted MKN45 cells were significantly decreased in Honokiol-treated mice and that endoplasmic reticulum (ER) stress was induced. Honokiol-treated tumors showed increased epithelial signatures such as E-cadherin, cytokeratin-18 and ER stress marker. In contrast, decreased expression of vimentin, Snail and tumor progression locus 2 (Tpl2) was also noted. TGFβ1 and MNNG-induced downregulation of E-cadherin and upregulation of Tpl2 were abrogated by Honokiol treatment. The effect of Tpl2 inhibition in cancer cells or endothelial cells was associated with inactivation of CCAAT/enhancer binding protein B, nuclear factor kappa-light-chain-enhancer of activated B cell and activator protein-1 and suppression of vascular endothelial growth factor. Inhibition of Tpl2 in gastric cancer cells by small interfering RNA or pharmacological inhibitor was found to effectively reduce growth ability and vessel density in vivo. Honokiol-induced reversal of epithelial-to-mesenchymal transition (EMT) and ER stress-induced apoptosis via Tp12 may involve the paralleling processes. Taken together, our results suggest that the therapeutic inhibition of Tpl2 by Honokiol thwarts both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Blotting, Western; Cell Adhesion; Cell Movement; Cell Proliferation; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Immunoprecipitation; Lignans; Luciferases; Male; MAP Kinase Kinase Kinases; Mice; Mice, Inbred BALB C; Mice, Nude; Peritoneal Neoplasms; Phytotherapy; Proto-Oncogene Proteins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Tumor Cells, Cultured

2013
Dietary intake of lignans and risk of esophageal and gastric adenocarcinoma: a cohort study in Sweden.
    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2013, Volume: 22, Issue:2

    High intake of phytoestrogen lignans has been found to be associated with decreased risk of esophageal adenocarcinoma in our previous population-based case-control study in Sweden. To further evaluate this possible association, we tested the hypothesis of an inverse association between dietary lignan intake and risk of esophageal and gastric adenocarcinoma using a prospective design. In a population-based cohort study in Sweden, 81,670 participants who were cancer-free at baseline were followed up during 1998 to 2009. All participants completed a 96-item food frequency questionnaire (FFQ), which was used to assess dietary exposure to lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol, and syringaresinol). All cases of esophageal, gastroesophageal junctional, and gastric adenocarcinoma were identified through linkage to the Swedish Cancer Register. Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI), with adjustment for potential confounding factors. During an average follow-up of 9.9 years, a total of 211 cases were identified, including 83 cases of esophageal or junctional adenocarcinoma, and 128 cases of gastric adenocarcinoma. There was no statistically significant association between dietary intake of lignans and any of the studied adenocarcinomas. Compared with participants in the lowest quartile of lignan intake, the adjusted HR of the highest quartile was 0.96 (95% CI, 0.46-2.00; P(trend) = 0.70) for adenocarcinoma of the esophagus or gastroesophageal junction, and 0.89 (95% CI, 0.52-1.55: P(trend) = 0.78) for gastric adenocarcinoma. No clear support for a protective role of dietary intake of lignans in the development of esophageal or gastric adenocarcinoma was found.

    Topics: Adenocarcinoma; Aged; Aged, 80 and over; Case-Control Studies; Diet; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Lignans; Male; Middle Aged; Prognosis; Prospective Studies; Risk Factors; Stomach Neoplasms; Sweden

2013
Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways.
    International journal of oncology, 2012, Volume: 40, Issue:4

    Gastric cancer is the fourth most commonly diagnosed cancer with the second highest mortality rate worldwide. Surgery, chemotherapy and radiation therapy are generally used for the treatment of stomach cancer but only limited clinical response is shown by these therapies and still no effectual therapy for advanced gastric adenocarcinoma patients is available. Therefore, there is a need to identify other therapeutic agents against this life-threatening disease. Plants are considered as one of the most important sources for the development of anticancer drugs. Magnolol, a natural compound possesses anticancer properties. However, effects of Magnolol on human gastric cancer remain unexplored. The effects of Magnolol on the viability of SGC-7901 cells were determined by the MTT assay. Apoptosis, mitochondrial membrane potential and cell cycle were evaluated by flow cytometry. Protein expression of Bcl-2, Bax, caspase-3 and PI3K/Akt was analysed by Western blotting. Magnolol induced morphological changes in SGC-7901 cells and its cytotoxic effects were linked with DNA damage, apoptosis and S-phase arrest in a dose-dependent manner. Magnolol triggered the mitochondrial-mediated apoptosis pathway as shown by an increased ratio of Bax/Bcl-2, dissipation of mitochondrial membrane potential (ΔΨm), and sequential activation of caspase-3 and inhibition of PI3K/Akt. Additionally, Magnolol induced autophagy in SGC-7901 cells at high concentration but was not involved in cell death. Magnolol-induced apoptosis of SGC-7901 cells involves mitochondria and PI3K/Akt-dependent pathways. These findings provide evidence that Magnolol is a promising natural compound for the treatment of gastric cancer and may represent a candidate for in vivo studies of monotherapies or combination antitumor therapies.

    Topics: Adenocarcinoma; Apoptosis; bcl-2-Associated X Protein; Biphenyl Compounds; Caspase 3; Cell Growth Processes; Down-Regulation; Enzyme Activation; Humans; Lignans; Mitochondria; Phosphatidylinositol 3-Kinases; Platelet Aggregation Inhibitors; Proto-Oncogene Proteins c-bcl-2; S Phase; Signal Transduction; Stomach Neoplasms

2012
Dietary intake of lignans and risk of adenocarcinoma of the esophagus and gastroesophageal junction.
    Cancer causes & control : CCC, 2012, Volume: 23, Issue:6

    The strong male predominance in esophageal and gastroesophageal junctional adenocarcinoma remains unexplained. Sex hormonal influence has been suggested, but not proven. A protective role of dietary phytoestrogen lignans was hypothesized.. A Swedish nationwide population-based case-control study was conducted in 1995-1997, including 181 cases of esophageal adenocarcinoma, 255 cases of gastroesophageal junctional adenocarcinoma, 158 cases of esophageal squamous cell carcinoma, and 806 control subjects. Data on various exposures, including dietary data, were collected through personal interviews and questionnaires. Dietary intake of lignans was assessed using a food frequency questionnaire and categorized into quartiles based on the consumption among the control participants. Unconditional logistic regression was used to calculate odds ratios (ORs) with 95 % confidence intervals (CIs), including adjustment for all established risk factors.. Participants in the highest quartile of intake of lignans compared with the lowest quartile were at a decreased risk of esophageal adenocarcinoma (OR, 0.65; 95 % CI, 0.38-1.12; p for trend =0.03), gastroesophageal junctional adenocarcinoma (OR, 0.37; 95 % CI, 0.23-0.58; p for trend <0.0001), and these adenocarcinomas combined (OR, 0.45; 95 % CI, 0.31-0.67; p for trend <0.0001). No clear associations were found between lignan intake and risk of esophageal squamous cell carcinoma.. This population-based study indicates that a high dietary intake of lignans decreases the risk of adenocarcinoma of the esophagus and gastroesophageal junction.

    Topics: Adenocarcinoma; Aged; Carcinoma, Squamous Cell; Case-Control Studies; Diet; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Lignans; Logistic Models; Male; Middle Aged; Odds Ratio; Phytoestrogens; Risk Factors; Stomach Neoplasms; Sweden

2012
Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice.
    PloS one, 2012, Volume: 7, Issue:8

    Honokiol, a small-molecular weight natural product, has previously been reported to activate apoptosis and inhibit gastric tumorigenesis. Whether honokiol inhibits the angiogenesis and metastasis of gastric cancer cells remains unknown.. We tested the effects of honokiol on angiogenic activity and peritoneal dissemination using in vivo, ex vivo and in vitro assay systems. The signaling responses in human gastric cancer cells, human umbilical vascular endothelial cells (HUVECs), and isolated tumors were detected and analyzed. In a xenograft gastric tumor mouse model, honokiol significantly inhibited the peritoneal dissemination detected by PET/CT technique. Honokiol also effectively attenuated the angiogenesis detected by chick chorioallantoic membrane assay, mouse matrigel plug assay, rat aortic ring endothelial cell sprouting assay, and endothelial cell tube formation assay. Furthermore, honokiol effectively enhanced signal transducer and activator of transcription (STAT-3) dephosphorylation and inhibited STAT-3 DNA binding activity in human gastric cancer cells and HUVECs, which was correlated with the up-regulation of the activity and protein expression of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1). Calpain-II inhibitor and siRNA transfection significantly reversed the honokiol-induced SHP-1 activity. The decreased STAT-3 phosphorylation and increased SHP-1 expression were also shown in isolated peritoneal metastatic tumors. Honokiol was also capable of inhibiting VEGF generation, which could be reversed by SHP-1 siRNA transfection.. Honokiol increases expression and activity of SPH-1 that further deactivates STAT3 pathway. These findings also suggest that honokiol is a novel and potent inhibitor of angiogenesis and peritoneal dissemination of gastric cancer cells, providing support for the application potential of honokiol in gastric cancer therapy.

    Topics: Animals; Apoptosis; Biphenyl Compounds; Calpain; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Mice; Neovascularization, Pathologic; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 6; RNA, Small Interfering; Signal Transduction; STAT3 Transcription Factor; Stomach Neoplasms; Up-Regulation; Xenograft Model Antitumor Assays

2012
Interaction effects between genes involved in the AKT signaling pathway and phytoestrogens in gastric carcinogenesis: a nested case-control study from the Korean Multi-Center Cancer Cohort.
    Molecular nutrition & food research, 2012, Volume: 56, Issue:11

    To investigate whether genes involved in AKT/nuclear factor kappa B signaling and/or gene-environment interactions between the genes and phytoestrogens may be susceptible factors for gastric cancer.. The representative single nucleotide polymorphisms (SNPs) identified during the primary analysis (screening a total of 622 SNPs within ± 5 kbp of the 51 target gene locations) were further investigated in 317 matched case-control sets. The summary odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer were calculated. Interaction effects between the SNPs and phytoestrogen biomarkers (genistein, daidzein, equol, and enterolactone) were computed. CDK1 rs4145643, FAS rs6586161, and FAS rs1468063 in the AKT signaling pathway presented significant genetic effects on gastric cancer (OR = 0.81 (95% CI: 0.66-0.99) for CDK1 rs4145643; OR = 1.27 (95% CI: 1.03-1.58) for FAS rs6586161; OR = 1.29 (95% CI: 1.03-1.56) for FAS rs1468063; Cochran Q statistics > 0.10). Risk alleles of FAS rs6586161, FAS rs1468063, MAP3K1 rs16886448, and MAP3K1 rs252902 showed significant interaction effects with enterolactone (p(interaction) < 0.05).. CDK1 and FAS genes involved in AKT signaling and influenced by anti-carcinogenic property of phytoestrogens can play a role as susceptible genetic factors in gastric carcinogenesis. FAS and MAP3K1 genes significantly interact with enterolactone, thereby modifying the individual's risk for gastric cancer.

    Topics: 4-Butyrolactone; Aged; Anticarcinogenic Agents; Asian People; Case-Control Studies; CDC2 Protein Kinase; Equol; fas Receptor; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Genistein; Humans; Isoflavones; Lignans; Male; MAP Kinase Kinase Kinase 1; Middle Aged; Odds Ratio; Phytoestrogens; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-akt; Republic of Korea; Signal Transduction; Stomach Neoplasms

2012
Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
    The American journal of clinical nutrition, 2012, Volume: 96, Issue:6

    Several experimental studies have suggested potential anticarcinogenic effects of flavonoids, although epidemiologic evidence for the impact of dietary flavonoids on risk of gastric cancer (GC) is limited.. We investigated the association between intake of dietary flavonoids and lignans and incident GC.. The study followed 477,312 subjects (29.8% men) aged 35-70 y from 10 European countries who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Validated dietary questionnaires and lifestyle information were collected at baseline. A food-composition database on flavonoids and lignans was compiled by using data from USDA and Phenol-Explorer databases.. During an average follow-up of 11 y, 683 incident GC cases (57.8% men) were mostly validated by a panel of pathologists and used in this analysis. We observed a significant inverse association between total flavonoid intake and GC risk in women (HR: 0.81; 95% CI: 0.70, 0.94; for the continuous variable after log₂ transformation) but not in men (HR: 0.97; 95% CI: 0.85, 1.09). In women, significant inverse associations with GC risk were also observed for intakes of some flavonoid subgroups (anthocyanidins, flavonols, flavones, and flavanols), particularly with intestinal type tumors for total flavonoid and flavanol intakes (P-heterogeneity < 0.1). After stratification by smoking status and sex, there was no significant heterogeneity in these associations between ever- and never-smokers.. Total dietary flavonoid intake is associated with a significant reduction in the risk of GC in women.

    Topics: Adenocarcinoma; Adult; Aged; Anticarcinogenic Agents; Cohort Studies; Diet; Europe; Female; Flavonoids; Follow-Up Studies; Humans; Incidence; Life Style; Lignans; Male; Middle Aged; Prospective Studies; Risk; Sex Factors; Stomach Neoplasms

2012
Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells.
    International immunopharmacology, 2011, Volume: 11, Issue:10

    Gastric cancer is a leading cause of cancer-related deaths, worldwide being second only to lung cancer as a cause of death. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms of arctigenin for anti-tumor effect on gastric cancer have not been examined. This study examined the biological effects of arctigenin on the human gastric cancer cell line SNU-1 and AGS. Cell proliferation was determined by MTT assay. In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by arctigenin in a time and dose dependent manner, as compared with SNU-1 and AGS cells cultured in the absence of arctigenin. Inhibition of cell proliferation by arctigenin was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bcl-2 to Bax by arctigenin. Also, arctigenin blocked cell cycle arrest from G(1) to S phase by regulating the expression of cell cycle regulatory proteins such as Rb, cyclin D1, cyclin E, CDK4, CDK2, p21Waf1/Cip1 and p15 INK4b. The antiproliferative effect of arctigenin on SNU-1 and AGS gastric cancer cells revealed in this study suggests that arctigenin has intriguing potential as a chemopreventive or chemotherapeutic agent.

    Topics: Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Furans; Humans; Lignans; Phosphorylation; Plants; Proto-Oncogene Proteins c-bcl-2; Retinoblastoma Protein; Stomach Neoplasms

2011
Effects of diphyllin as a novel V-ATPase inhibitor on gastric adenocarcinoma.
    European journal of pharmacology, 2011, Sep-30, Volume: 667, Issue:1-3

    The natural compound diphyllin, a cytostatic lignan isolated from Cleistanthus collinus, can dramatically inhibit the proliferation and induce the apoptosis of human gastric cancer cells, SGC7901. Our study found that diphyllin can inhibit the expression of V-ATPases in a dose-dependent manner, decrease the internal pH (pHi) and reverse the transmembrane pH gradient in SGC7901 cells. Changes of the pH gradient were positively correlated with diphyllin concentration. Further study found that diphyllin treatment caused a decrease in phospho-LRP6, but not in LRP6. β-catenin in Wnt/β-catenin signaling and its target genes, c-myc and cyclin-D1, were also decreased with the inhibition of V-ATPases. Therefore, diphyllin could be characterized as a new V-ATPase inhibitor in treating gastric cancer and inhibiting the phosphorylation of LRP6 in Wnt/β-catenin signaling.

    Topics: Adenocarcinoma; Animals; Apoptosis; Benzodioxoles; Cell Line, Tumor; Cell Proliferation; Dioxolanes; Enzyme Inhibitors; Extracellular Space; Humans; Hydrogen-Ion Concentration; Intracellular Space; Lignans; Low Density Lipoprotein Receptor-Related Protein-6; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; Stomach Neoplasms; Vacuolar Proton-Translocating ATPases; Xenograft Model Antitumor Assays

2011
Phenolic compounds as selective antineoplasic agents against multidrug-resistant human cancer cells.
    Planta medica, 2010, Volume: 76, Issue:10

    Twelve phenolic compounds, including three stilbenes, two flavonoids, two coumarins, one neolignan, and four lignans, isolated from Euphorbia and Pycnanthus species or obtained by derivatization, were assayed for their potential antineoplastic efficacy in three human cancer cell lines: gastric (EPG85-257), pancreatic (EPP85-181), and colon (HT-29) carcinomas as well as derived multidrug-resistant sublines. In each case, two different multidrug-resistant variants, i.e., cell lines with classical and atypical MDR phenotype, were used. The majority of the MDR cancer sublines showed increased sensitivities to the studied compounds when compared to the parental sublines. The most active compound was the flavonoid naringenin, found to be 15-fold more effective against the atypical MDR subline of gastric carcinoma than in parental drug-sensitive cells. Furthermore, the stilbene trans-3,5,3',4'-tetramethoxypiceatannol and the lignans 4'-hydroxy-3,3',4-trimethoxylignan and heliobuphthalmin also exhibited high antineoplasic activities against the classical MDR subline derived from gastric carcinoma. The results of this study suggest that some phenolic compounds might be valuable for the treatment of multidrug-resistant cancer cells.

    Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Colonic Neoplasms; Drug Resistance, Multiple; Euphorbia; Flavanones; Humans; Lignans; Magnoliopsida; Myristicaceae; Neoplasms; Pancreatic Neoplasms; Phenols; Phytotherapy; Plant Extracts; Stilbenes; Stomach Neoplasms

2010
Honokiol inhibits gastric tumourigenesis by activation of 15-lipoxygenase-1 and consequent inhibition of peroxisome proliferator-activated receptor-gamma and COX-2-dependent signals.
    British journal of pharmacology, 2010, Volume: 160, Issue:8

    Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), COX-2 and 15-lipoxygenase (LOX)-1 have been shown to be involved in tumour growth. However, the roles of PPAR-gamma, COX-2 or 15-LOX-1 in gastric tumourigenesis remain unclear. Here, we investigate the role of 15-LOX-1 induction by honokiol, a small-molecular weight natural product, in PPAR-gamma and COX-2 signalling during gastric tumourigenesis.. Human gastric cancer cell lines (AGS, MKN45, N87 and SCM-1) were cultured with or without honokiol. Gene and protein expressions were analysed by RT-PCR and Western blotting respectively. Small interfering RNAs (siRNAs) for COX-2, PPAR-gamma and 15-LOX-1 were used to interfere with the expressions of these genes. A xenograft gastric tumour model in mouse was used for in vivo study.. PPAR-gamma and COX-2 proteins were highly expressed in gastric cancer cells. Inhibitors, or siRNA for COX-2 or PPAR-gamma, significantly decreased cell viability. Honokiol markedly inhibited PPAR-gamma and COX-2 expressions in gastric cancer cells and tumours of xenograft mice, and induced apoptosis and cell death. Honokiol markedly activated cellular 15-LOX-1 expression and 13-S-hydroxyoctadecadienoic acid (a primary product of 15-LOX-1 metabolism of linoleic acid) production. 15-LOX-1 siRNA could reverse the honokiol-induced down-regulation of PPAR-gamma and COX-2, and cell apoptosis. 15-LOX-1 was markedly induced in tumours of xenograft mice treated with honokiol.. These findings suggest that induction of 15-LOX-1-mediated down-regulation of a PPAR-gamma and COX-2 pathway by honokiol may be a promising therapeutic strategy for gastric cancer.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Arachidonate 15-Lipoxygenase; Biphenyl Compounds; Blotting, Western; Cell Line, Tumor; Cell Survival; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Enzyme Activation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lignans; Linoleic Acids; Male; Mice; Mice, Inbred BALB C; Mice, Nude; PPAR gamma; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Signal Transduction; Stomach Neoplasms; Time Factors; Tumor Burden; Xenograft Model Antitumor Assays

2010
Inhibitory effect of nordihydroguaiaretic acid, a plant lignan, on Helicobacter pylori-associated gastric carcinogenesis in Mongolian gerbils.
    Cancer science, 2007, Volume: 98, Issue:11

    Recent epidemiological studies have demonstrated that consumption of certain natural products can lower cancer risk in humans. For example, plant-derived lignans have been shown to exert chemopreventive effects against cancer in vitro and in vivo. In the present study, the effects of three such lignans, termed arctiin, arctigenin, and nordihydroguaiaretic acid (NDGA), on the proliferation of Helicobacter pylori and the prevention of H. pylori-associated gastric cancer were investigated in Mongolian gerbils. To examine the effects of arctigenin and NDGA on stomach carcinogenesis, specific pathogen-free male, 5-week-old gerbils were infected with H. pylori, administered 10 p.p.m. N-methyl-N-nitrosourea in their drinking water and fed diets containing various concentrations of lignans until they were killed after 52 weeks. At a dietary level of 0.25%, NDGA significantly decreased the incidence of gastric adenocarcinomas. Arctigenin, in contrast, failed to attenuate neoplasia at a level of 0.1%. Both NDGA and arctigenin significantly reduced serum 8-hydroxy-2'-deoxyguanosine levels at doses of 0.25 and 0.05% (NDGA), and 0.1% (arctigenin). Administration of 0.25% NDGA significantly suppressed the formation of intestinal metaplasia both in the antrum and the corpus. Although all three lignans dose-dependently inhibited the in vitro proliferation of H. pylori, there were no differences in the titers of anti-H. pylori antibodies or the amount of the H. pylori-specific urease A gene among all H. pylori-infected groups. These results suggest that NDGA might be effective for prevention of gastric carcinogenesis. The possible mechanisms appear to be related to inhibitory effects on progression of gastritis and antioxidative activity rather than direct antimicrobial influence.

    Topics: Adenocarcinoma; Animals; Cell Division; Disease Models, Animal; Furans; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Lignans; Male; Masoprocol; Plants; Polymerase Chain Reaction; Specific Pathogen-Free Organisms; Stomach Neoplasms; Urease

2007
Honokiol induces calpain-mediated glucose-regulated protein-94 cleavage and apoptosis in human gastric cancer cells and reduces tumor growth.
    PloS one, 2007, Oct-31, Volume: 2, Issue:10

    Honokiol, a small molecular weight natural product, has been shown to possess potent anti-neoplastic and anti-angiogenic properties. Its molecular mechanisms and the ability of anti-gastric cancer remain unknown. It has been shown that the anti-apoptotic function of the glucose-regulated proteins (GRPs) predicts that their induction in neoplastic cells can lead to cancer progression and drug resistance. We explored the effects of honokiol on the regulation of GRPs and apoptosis in human gastric cancer cells and tumor growth.. Treatment of various human gastric cancer cells with honokiol led to the induction of GRP94 cleavage, but did not affect GRP78. Silencing of GRP94 by small interfering RNA (siRNA) could induce cell apoptosis. Treatment of cells with honokiol or chemotherapeutics agent etoposide enhanced the increase in apoptosis and GRP94 degradation. The calpain activity and calpain-II (m-calpain) protein (but not calpain-I (micro-calpain)) level could also be increased by honokiol. Honokiol-induced GRP94 down-regulation and apoptosis in gastric cancer cells could be reversed by siRNA targeting calpain-II and calpain inhibitors. Furthermore, the results of immunofluorescence staining and immunoprecipitation revealed a specific interaction of GRP94 with calpain-II in cells following honokiol treatment. We next observed that tumor GRP94 over-expression and tumor growth in BALB/c nude mice, which were inoculated with human gastric cancer cells MKN45, are markedly decreased by honokiol treatment.. These results provide the first evidence that honokiol-induced calpain-II-mediated GRP94 cleavage causes human gastric cancer cell apoptosis. We further suggest that honokiol may be a possible therapeutic agent to improve clinical outcome of gastric cancer.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Calpain; Cell Line, Tumor; Endoplasmic Reticulum Chaperone BiP; Glucose; Humans; Kinetics; Lignans; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Models, Biological; Stomach Neoplasms

2007
Inhibitory effect of schisandrin B on gastric cancer cells in vitro.
    World journal of gastroenterology, 2007, Dec-28, Volume: 13, Issue:48

    To investigate the inhibitory effect and possible mechanism of action of schisandrin B in SC-B on gastric cancer cells in vitro.. SC-B consisted of schisandrin B, aloe-emodin, and Astragalus polysaccharides. Exponentially growing human gastric cancer SGC-7901 cells were divided into six treatment groups: (1) control group (RPMI 1640 medium); (2) negative control group (2% DMSO); (3) positive control group (50 mg/L 5-Fluorouracil, 5-FU); (4) low-dose group (LSC, final concentration of schisandrin B, 25 mg/L); (5) moderate-dose group (MSC, final concentration of schisandrin B, 50 mg/L); (6) high-dose group (HSC, final concentration of schisandrin B, 100 mg/L). Follow-up was done at 12-48 h. An MTT (Methylthiazolyldiphenyl-tetrazolium bromide) assay was used to examine the inhibitory effect of SC-B on gastric cancer cells. The mitosis index was assessed using an inverted microscope. Flow cytometry was used to visualize the cell cycle. An RT-PCR (Reverse transcription-Polymerase chain reaction) -based assay was used to detect mRNA expression for cyclin D1 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).. The MTT assay showed that the number of living cells in the LSC, MSC and HSC groups was significantly smaller than that in the DMSO-treated group (P < 0.05) at 12-48 h. The inhibitory rate (IR) of the LSC group was 41.15% +/- 3.86%, 59.24% +/- 5.34% and 69.93% +/- 7.81% at 12, 24 and 48 h, respectively. The IR of the MSC group was 42.82% +/- 4.94%, 62.68% +/- 7.58% and 71.79% +/- 8.12% at 12, 24 and 48 h, respectively. The IR of the HSC group was 37.50% +/- 3.21%, 40.34% +/- 2.98% and 61.99% +/- 4.88% at 12, 24 and 48 h, respectively. These results suggested that a moderate dosage had the most obvious inhibitory efficacy at 48 h. Compared to the DMSO group, the mitosis index of the LSC, MSC, HSC groups was greatly decreased (P < 0.05) at all time points. Any dose of SC-B suppressed mitosis within 12-48 h. Compared to the DMSO group, the percentage of cells in the G0/G1 phase of the MSC group was greatly increased, and that of the S + G2M phase was greatly decreased, while the percentage of cell inhibition (PCI) in the MSC group was greatly increased (P < 0.05). This suggested that SC-B could exclusively arrest cells in the G0/G1 phase. Cyclin D1 mRNA expression was lower in the MSC group than that in the DMSO group (P < 0.05).. SC-B can inhibit the proliferation and aberrant mitosis of human gastric cancer SCG-7901 cells in vitro. This inhibitory effect may be due to the down-regulation of cyclin D1 mRNA expression, which causes cell cycle arrest of gastric cancer cells.

    Topics: Astragalus Plant; Cell Cycle; Cell Line, Tumor; Cyclin D1; Cyclooctanes; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Emodin; Glucosides; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Lignans; Medicine, Chinese Traditional; Mitosis; Polycyclic Compounds; Polysaccharides; RNA, Messenger; Stomach Neoplasms; Time Factors

2007