Association between Polyphenol Intake and Gastric Cancer Risk by Anatomic and Histologic Subtypes: MCC-Spain

Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from different regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed effects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (ORQ4 vs. Q1 = 0.47; 95% CI: 0.32–0.69 and ORQ4 vs. Q1 = 0.53; 95% CI: 0.36–0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (ORQ4 vs. Q1 = 0.41; 95% CI: 0.28–0.61), hydroxycoumarins (ORQ4 vs. Q1 = 0.49; 95% CI: 0.34–0.71), and tyrosols (ORQ4 vs. Q1 = 0.56; 95% CI: 0.39–0.80) were inversely associated with GC risk. No differences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results.

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The In Vivo Antioxidant and Hepatoprotective Actions of Selected Chinese Teas

Foods ◽

10.3390/foods9030262 ◽

2020 ◽

Vol 9 (3) ◽

pp. 262

Author(s):

Shi-Yu Cao ◽

Bang-Yan Li ◽

Ren-You Gan ◽

Qian-Qian Mao ◽

Yuan-Feng Wang ◽

...

Keyword(s):

Antioxidant Activity ◽

Antioxidant Activities ◽

In Vitro Study ◽

Total Phenolic ◽

Gallocatechin Gallate ◽

Dietary Components ◽

The Relationship ◽

In Vitro Antioxidant Activity

Tea is a popular beverage and shows very strong in vitro antioxidant activity. However, the relationship among in vitro and in vivo antioxidant activities in teas is seldom reported. In this study, in vivo antioxidant and hepatoprotective activities of 32 selected Chinese teas were evaluated on a mouse model with acute alcohol-induced liver injury. The results showed that most teas significantly reduced the levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, triacylglycerol, and total bilirubin in the sera of mice at a dose of 400 mg/kg. In addition, most teas greatly decreased the malondialdehyde level and increased the levels of superoxide dismutase, glutathione peroxidase, and glutathione in the liver of mice, indicating the antioxidant and hepatoprotective activities of teas. Furthermore, the in vivo antioxidant activity of dark tea was stronger than that of green tea, opposite to the results of the in vitro study. Among these 32 teas, Black Fu Brick Tea, Pu-erh Tea, and Qing Brick Tea showed the strongest antioxidant and hepatoprotective activities. Moreover, total phenolic content as well as the contents of epicatechin, gallocatechin gallate, and chlorogenic acid were found to contribute, at least partially, to the antioxidant and hepatoprotective actions of these teas. Overall, teas are good dietary components with antioxidant and hepatoprotective actions.

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HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4

Frontiers in Oncology ◽

10.3389/fonc.2021.645979 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhengqian Chen ◽

Zhiwei Qin ◽

Lei Li ◽

Qi Wo ◽

Xia Chen

Keyword(s):

Gastric Cancer ◽

Underlying Mechanism ◽

Cell Counting ◽

Luciferase Reporter ◽

Sequencing Analysis ◽

Kaplan Meier ◽

The Relationship ◽

Kaplan Meier Plotter

PurposeChemoresistance remains a major challenge in the therapy of gastric cancer (GC). The homeobox (HOX) gene family has gained attention in carcinogenesis and chemoresistance. Here, this study aimed to explore the mechanism of HOXA13 in GC chemoresistance.MethodsQuantitative real-time PCR (qRT-PCR) and Western blot were used to evaluate the expression of HOXA13 in GC tissues. The Kaplan–Meier plotter database was mined for prognosis analysis of GC patients with different HOXA13 expression receiving 5-Fluorouracil (5-FU) therapy. The effects of HOXA13 on sensitivity of GC cells to 5-FU were investigated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2’-deoxyuridine (EdU) incorporation, flow cytometry and experiment in vivo. RNA-Sequencing analysis was performed to explore the underlying mechanism of HOXA13-mediated 5-FU resistance in GC. Chromatin immunoprecipitation (ChIP) and rescue experiments were applied to determine the relationship between HOXA13 and ABCC4. Luciferase reporter assay was performed to assess interaction of miR-139-5p and HOXA13.ResultsHOXA13 was upregulated in GC and its high expression was associated with poor prognosis of GC patients with 5-FU treatment. Overexpression of HOXA13 impaired the inhibitory effects of 5-FU on GC cells proliferation in vitro and vivo, and knockdown of HOXA13 exacerbated 5-FU-induced GC cells apoptosis. Mechanistically, HOXA13, directly targeted by miR-139-5p in GC, might upregulate ABCC4 expression, thereby accentuating 5-FU resistance of GC cells.ConclusionOur study suggests that HOXA13 attenuates 5-FU sensitivity of GC possibly by upregulating ABCC4. Thus, targeting HOXA13 would provide a novel prospective into the potential therapeutic strategy for reversing chemoresistance.

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A Decade of Research on Coffee as an Anticarcinogenic Beverage

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/4420479 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Ayelén D. Nigra ◽

Anderson J. Teodoro ◽

Germán A. Gil

Keyword(s):

Protective Factor ◽

Coffee Consumption ◽

In Vivo Studies ◽

Inverse Association ◽

Phytochemical Content ◽

Coffee Drinking ◽

Anticancer Properties ◽

General Studies

Coffee consumption has been investigated as a protective factor against cancer. Coffee is a complex beverage that contains more than 1000 described phytochemicals, which are responsible for its pleasant taste, aroma, and health-promoting properties. Many of these compounds have a potential therapeutic effect due to their antioxidant, anti-inflammatory, antifibrotic, and anticancer properties. The roasting process affects the phytochemical content, and undesirable compounds may be formed. In recent years, there have been contradictory publications regarding the effect of coffee drinking and cancer. Therefore, this study is aimed at evaluating the association of coffee consumption with the development of cancer. In PubMed, until July 2021, the terms “Coffee and cancer” resulted in about 2150 publications, and almost 50% of them have been published in the last 10 years. In general, studies published in recent years have shown negative associations between coffee consumption and the risk or development of different types of cancer, including breast, prostate, oral, oral and pharyngeal, melanoma, skin and skin nonmelanoma, kidney, gastric, colorectal, endometrial, liver, leukemic and hepatocellular carcinoma, brain, and thyroid cancer, among others. In contrast, only a few publications demonstrated a double association between coffee consumption and bladder, pancreatic, and lung cancer. In this review, we summarize the in vitro and in vivo studies that accumulate epidemiological evidence showing a consistent inverse association between coffee consumption and cancer.

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Knockdown of KREMEN2 inhibits tumor proliferation and metastasis in gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16555 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16555-e16555

Author(s):

Beibei Chen ◽

Saiqi Wang ◽

Jinxi Huang ◽

Jitian Li ◽

Jianying Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Gastric Cancer Cell ◽

Akt Pathway ◽

Gastric Cancer Cells ◽

The Relationship

e16555 Background: KREMEN2 is an important regulator of classical Wnt/β-catenin signaling pathway. However, the relationship between KREMEN2 and gastric cancer is not clear. The aim of this study was to explore the regulatory role of KREMEN2 in the tumorigenesis and metastasis of gastric cancer. Methods: We measured the protein level of KREMEN2 in 156 gastric adenocarcinoma, 40 metastatic gastric adenocarcinoma, 8 marginal and 4 normal tissues using tissue microarray. The differences in KREMEN2 expression were tested with Mann-Whitney U test. The relationship between KREMEN2 expression and pathologic data was determined with Pearson’s correlation analysis. The mRNA and protein level in cultured cell lines were detected by qRT-PCR and western blotting, respectively. Lentivirus was transfected by repressing KREMEN2. Cell viability was determined by the MTT assay. Apoptosis and cell cycle distribution were detected using flow cytometry. The cell migration was investigated by wound healing and transwell assay. Antibody array was performed to explore the underlying molecule mechanism. In vivo, Xenograft assay was established using nude mice to explore the role of KREMEN2 in gastric cancer cell and bioluminescence was observed via an in vivo imaging system. Results: It was demonstrated that, compared to para-cancerous tissues, KREMEN2 was significantly up-regulated in gastric cancer tissues, and was positively correlated with the pathological grade of gastric cancer patients. Given that KREMEN2 is abundantly expressed in most tested gastric cancer cell lines, KREMEN2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down KREMEN2, the proliferation of gastric cancer cells was inhibited both in vivo and in vitro. At the same time, knockdown of KREMEN2 induced apoptosis, cell cycle arrest at G2/M phase and inhibition of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of KREMEN2 suppressed PI3K/Akt pathway. Conclusions: Therefore, we revealed that the overexpression of KREMEN2 in gastric cancer may promote the carcinogenesis and metastasis of gastric cancer by activating the PI3K/Akt pathway.

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Total polyphenol intake and breast cancer risk in the Seguimiento Universidad de Navarra (SUN) cohort

British Journal Of Nutrition ◽

10.1017/s0007114518003811 ◽

2019 ◽

Vol 122 (5) ◽

pp. 542-551 ◽

Cited By ~ 5

Author(s):

Itziar Gardeazabal ◽

Andrea Romanos-Nanclares ◽

Miguel Ángel Martínez-González ◽

Rodrigo Sánchez-Bayona ◽

Facundo Vitelli-Storelli ◽

...

Keyword(s):

Breast Cancer ◽

University Graduates ◽

Inverse Association ◽

Total Polyphenol ◽

Cox Models ◽

Hazard Ratios ◽

Food Consumption Data ◽

Polyphenol Intake

AbstractPolyphenols are a wide family of phytochemicals present in diverse foods. They might play a role in cancer development and progression.In vivoandin vitrostudies have suggested beneficial properties and potential mechanisms. We aimed to evaluate the association between total and main classes of polyphenol intake and breast cancer (BC) risk in the Seguimiento Universidad de Navarra project – a prospective Mediterranean cohort study. We included 10 713 middle-aged, Spanish female university graduates. Polyphenol intake was derived from a semi-quantitative FFQ and matching food consumption data from the Phenol-Explorer database. Women with self-reported BC were asked to return a copy of their medical report for confirmation purposes; death certificates were used for fatal cases. Cox models were fitted to estimate multivariable-adjusted hazard ratios (HR) and 95 % CI for the association between tertiles (T) of polyphenol intake and BC. After 10·3 years of median follow-up, 168 probable incident BC cases were identified, out of which 100 were confirmed. We found no association between polyphenol intake and the overall BC risk. Nevertheless, we observed a significant inverse association between total polyphenol intake and BC risk for postmenopausal women, either for probable or only for confirmed cases (HRT3v.T10·31 (95 % CI 0·13, 0·77;Ptrend=0·010)). Also, phenolic acid intake was inversely associated with postmenopausal BC. In summary, we observed no significant association between total polyphenol intake and BC risk. Despite a low number of incident BC cases in our cohort, higher total polyphenol intake was associated with a lower risk of postmenopausal BC.

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FGFR2 Promotes Gastric Cancer Progression by Inhibiting the Expression of Thrombospondin4 via PI3K-Akt-Mtor Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000494590 ◽

2018 ◽

Vol 50 (4) ◽

pp. 1332-1345 ◽

Cited By ~ 14

Author(s):

Tingting Huang ◽

Dian Liu ◽

Yihua Wang ◽

Piao Li ◽

Li Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Clinical Stage ◽

Xenograft Model ◽

Mtor Pathway ◽

Invasion And Migration ◽

And Migration ◽

The Relationship

Background/Aims: Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC. Methods: Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model. Results: FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis. Conclusion: The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2.

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Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053711 ◽

1982 ◽

Vol 40 ◽

pp. 210-211

Author(s):

M.J. Murphy ◽

R.R. Price ◽

J.C. Sloman

Keyword(s):

Cultured Cells ◽

Human Tumor ◽

Cell Type ◽

Tumor Mass ◽

Initial Cell ◽

Cloning Assay ◽

Human Tumor Cloning ◽

The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

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Vitamin D as potential therapeutic anticancer agent

Journal of Cancer Science and Therapeutics ◽

10.36879/jcst.19.000106 ◽

2018 ◽

pp. 1-3

Keyword(s):

Vitamin D ◽

Anticancer Activity ◽

Anticancer Agent ◽

Antitumor Agents ◽

Metastatic Potential ◽

Anticancer Properties ◽

Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

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A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180917100640 ◽

2018 ◽

Vol 18 (17) ◽

pp. 1483-1493

Author(s):

Ricardo Imbroisi Filho ◽

Daniel T.G. Gonzaga ◽

Thainá M. Demaria ◽

João G.B. Leandro ◽

Dora C.S. Costa ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Hepatic Function ◽

Anticancer Properties ◽

Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

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Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (α-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities

Foods ◽

10.3390/foods10020315 ◽

2021 ◽

Vol 10 (2) ◽

pp. 315

Author(s):

Zhenxing Wang ◽

Zongcai Tu ◽

Xing Xie ◽

Hao Cui ◽

Kin Weng Kong ◽

...

Keyword(s):

Ethyl Acetate ◽

Animal Experiments ◽

Ethyl Acetate Fraction ◽

The Body ◽

Total Phenolic ◽

Antioxidant Power ◽

Glycogen Accumulation ◽

Inhibitory Ability

This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid–liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 μg GAE/mg DE) and flavonoid content (455.22 μg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful α-glucosidase inhibitory ability with the IC50 value of 190.03 μg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC50 values of 37.92 and 13.43 μg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.

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