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https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#1
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28317866/cyclooxygenase-2-facilitates-dengue-virus-replication-and-serves-as-a-potential-target-for-developing-antiviral-agents
#2
Chun-Kuang Lin, Chin-Kai Tseng, Yu-Hsuan Wu, Chih-Chuang Liaw, Chun-Yu Lin, Chung-Hao Huang, Yen-Hsu Chen, Jin-Ching Lee
Cyclooxygenase-2 (COX-2) is one of the important mediators of inflammation in response to viral infection, and it contributes to viral replication, for example, cytomegalovirus or hepatitis C virus replication. The role of COX-2 in dengue virus (DENV) replication remains unclear. In the present study, we observed an increased level of COX-2 in patients with dengue fever compared with healthy donors. Consistent with the clinical data, an elevated level of COX-2 expression was also observed in DENV-infected ICR suckling mice...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28314282/comparison-of-the-effects-of-monastrol-and-oxomonastrol-on-human-hepatoma-cell-line-hepg2-c3a
#3
Lilian Areal Marques, Simone Cristine Semprebon, Daniele Sartori, Ângelo DE Fátima, Lúcia Regina Ribeiro, Mário Sérgio Mantovani
Monastrol and its analog oxomonastrol differ by replacement of the sulfur atom present in monastrol to an oxygen atom in oxomonastrol. Monastrol inhibits the mitotic kinesin family member 11 (EG5), which has been studied for its potential use in cancer therapy. The aim of this study was to investigate the effect of monastrol and oxomonastrol on HepG2/C3A cells. Our results showed that monastrol induced DNA damage, reduced cell proliferation, and up-regulated the cytochrome P450 family 1 subfamily A member 1 (CYP1A1) mRNA levels...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314273/failure-of-inositol-trispyrophosphate-to-enhance-highly-effective-radiotherapy-of-gl261-glioblastoma-in-mice
#4
Sujatha Iyengar, David Schwartz
BACKGROUND/AIM: Inositol trispyrophosphate (ITPP), reported to cure hepatomas in a preclinical rat model and to have beneficial effects in several other solid tumor models, is currently in clinical trial for liver cancer. We investigated whether aggressive glioblastomas could be effectively treated with ITPP alone or in combination with radiation therapy (RT). MATERIALS AND METHODS: C57Bl/6 mice were intracranially injected with syngeneic GL261 glioblastoma cells and treated with hypofractionated radiation (5 Gy × 3), ITPP, or both...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28299863/dickkopf-3-attenuates-xanthine-dehydrogenase-expression-to-prevent-oxidative-stress-induced-apoptosis
#5
Shuang Qui, Junko Kano, Masayuki Noguchi
Dickkopf (DKK) 3 is a DKK glycoprotein family member that controls cell fate during embryogenesis and exerts opposing effects on survival in a cell type-dependent manner; however, the mechanisms governing its pro-apoptosis versus pro-survival functions remain unclear. Here, we investigated DKK3 function in Li21 hepatoma cells and tPH5CH immortalized hepatocytes. DKK3 knockdown by siRNA resulted in reactive oxygen species accumulation and subsequent apoptosis, which were abrogated by administration of the antioxidant N-acetyl-cysteine...
March 15, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28296595/time-course-effect-of-r-alpha-lipoic-acid-on-cellular-metabolomics-in-cultured-hepatoma-cells
#6
Naoko Ikuta, Keita Chikamoto, Yuya Asano, Yoshiaki Yasui, Haruka Yokokawa, Keiji Terao, Gerald Rimbach, Seiichi Matsugo
Alpha-lipoic acid (LA) is a powerful antioxidant. LA has two enantiomers, R(+)-LA (R-LA) and S(-)-LA (S-LA). Of these, R-LA is naturally occurring and an essential cofactor in energy metabolism. R-LA treatment has been reported to affect glucose metabolism in rat hepatoma cells. This study analyzed the time course of metabolite levels in LA-treated cultured H4IIEC3 rat hepatoma cells, including a specific evaluation of the effect of R-LA and the enantioselectivity of LA. Principal component analysis showed that this experiment was well designed to observe enantioselectivity...
March 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumor-growth-through-cd8-ctls-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#7
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Fiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumor-specific class I major histocompatibility complex (MHC-I) molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28291743/lactobionic-acid-conjugated-tpgs-nanoparticles-for-enhancing-therapeutic-efficacy-of-etoposide-against-hepatocellular-carcinoma
#8
Altansukh Tsend-Ayush, Xiumei Zhu, Yu Ding, Jianxu Yao, Lifang Yin, Zhou Jianping, Jing Yao
Many effective anticancer drugs are limited to use for hepatocellular carcinoma (HCC) therapy due to drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and inhibition of drug resistance-related mechanisms become an integrated strategy to combat effectively chemo-resistant cancer. Herein, lactobionic acid-conjugated D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) was developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC...
March 14, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28289825/the-highly-bioactive-molecule-and-signal-substance-6-formylindolo-3-2-b-carbazole-ficz-plays-bi-functional-roles-in-cell-growth-and-apoptosis-in-vitro
#9
Afshin Mohammadi-Bardbori, Farzaneh Bastan, Amin-Reza Akbarizadeh
The maintenance of cellular homeostasis is a complex process that is governed by the receipt of prototypical growth and death signals. The endogenous functions of aryl hydrocarbon receptor (AHR) in cellular homeostasis are not well understood. We aimed to establish whether the disturbance of endogenously activated AHR can influence cell growth, and if so, what mechanism(s) are involved. Cell growth was measured in mouse hepatoma Hepa-1 wild-type and cytochrome P4501A1 (CYP1A1)-deficient c37 cells. In other sets of experiments, HepG2 cells were exposed to different doses of FICZ (0...
March 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28286534/rosemary-extracts-upregulate-nrf2-sestrin2-and-mrp2-protein-level-in-human-hepatoma-hepg2-cells
#10
Xiao-Pei Tong, Yan-Xia Ma, Dan-Ni Quan, Ling Zhang, Miao Yan, Xin-Rong Fan
In the past few decades, the incidence of liver cancer has been rapidly rising across the world. Rosemary is known to possess antioxidant activity and is used as natural antioxidant food preservative. It is proposed to have anticancer activity in treating different tumor models. In this study, we try to explore the impact of rosemary extracts on upregulating the level of Nrf2 and Nrf2-regulatory proteins, Sestrin2 and MRP2 in HepG2 cells, and to speculate its potential mechanism. The anticancer activity of rosemary extract, including its polyphenolic diterpenes carnosic acid and carnosol, was evaluated to understand the potential effect on HepG2 cells...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28283039/hepatitis-c-virus-ns3-protein-enhances-hepatocellular-carcinoma-cell-invasion-by-promoting-ppm1a-ubiquitination-and-degradation
#11
Yali Zhou, Yan Zhao, Yaoying Gao, Wenjun Hu, Yan Qu, Ning Lou, Ying Zhu, Xiaoping Zhang, Hongmei Yang
BACKGROUND: Growing evidence suggests that hepatitis C virus (HCV) contributes to hepatocellular carcinoma (HCC) by directly modulating oncogenic signaling pathways. Protein phosphatase magnesium-dependent 1A (PPM1A) has recently emerged as an important tumor suppressor as it can block a range of tumor-centric signaling pathways through protein dephosphorylation. However, the role and regulatory mechanisms of PPM1A in HCV-infected cells have not been reported. METHODS: Total, cytoplasmic, and nuclear PPM1A protein after HCV infection or overexpression of HCV nonstructural protein 3 (NS3) were detected by western blotting...
March 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28279696/hydroxystilbenes-and-methoxystilbenes-activate-human-aryl-hydrocarbon-receptor-and-induce-cyp1a-genes-in-human-hepatoma-cells-and-human-hepatocytes
#12
Barbora Pastorková, Aneta Vrzalová, Petr Bachleda, Zdeněk Dvořák
Natural polyphenol resveratrol (trihydroxystilbene) is a partial agonist of human aryl hydrocarbon receptor AhR, thereby, displaying a plethora of biological effects. Biological activities of metoxylated and hydroxylated stilbenes were studied in the past. The aim of the current study was to describe the effects of 13 different hydroxy- and methoxystilbenes, including their cis/trans isomers on the transcriptional activity of AhR and the expression of CYP1A genes in hepatic cancer cells HepG2 and in primary human hepatocytes...
March 6, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28279180/primaquine-thiazolidinones-block-malaria-transmission-and-development-of-the-liver-exoerythrocytic-forms
#13
Anna Caroline C Aguiar, Flávio Jr B Figueiredo, Patrícia D Neuenfeldt, Tony H Katsuragawa, Bruna B Drawanz, Wilson Cunico, Photini Sinnis, Fidel Zavala, Antoniana U Krettli
BACKGROUND: Primaquine is an anti-malarial used to prevent Plasmodium vivax relapses and malaria transmission. However, PQ metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Fifteen PQ-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes. RESULTS: All primaquine derivatives (PQ-TZs) exhibited lower cell toxicity than primaquine; none caused haemolysis to normal or G6PD-deficient human erythrocytes in vitro...
March 9, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28278373/potential-metabolic-activation-of-a-representative-c4-alkylated-polycyclic-aromatic-hydrocarbon-retene-1-methyl-7-isopropyl-phenanthrene-associated-with-the-deepwater-horizon-oil-spill-in-human-hepatoma-hepg2-cells
#14
Meng Huang, Clementina A Mesaros, Linda C Hackfield, Richard P Hodge, Tianzhu Zang, Ian Alexander Blair, Trevor M Penning
Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) in the food-chain is the major human health hazard associated with the Deepwater Horizon oil spill. C4-Phenanthrenes are representative PPAHs present in the crude oil and could contaminate the seafood. We describe the metabolism of a C4-phenanthrene regioisomer retene (1-methyl-7-isopropyl-phenanthrene) in human HepG2 cells as a model for metabolism in human hepatocytes. Retene because of its sites of alkylation cannot be metabolized to a diol-epoxide...
March 9, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28276928/plectin-deficiency-in-liver-cancer-cells-promotes-cell-migration-and-sensitivity-to-sorafenib-treatment
#15
Chiung-Chi Cheng, Wei-Ting Chao, Chen-Chun Liao, Yu-Hui Tseng, Yen-Chang Clark Lai, Yih-Shyong Lai, Yung-Hsiang Hsu, Yi-Hsiang Liu
Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib...
February 17, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28276763/coumarins-from-the-bark-of-juglans-mandshurica-exhibited-anti-hepatoma-activities-via-inducing-apoptosis
#16
Guo-Dong Yao, Zhuo-Yang Cheng, Xin-Yue Shang, Pin-Yi Gao, Xiao-Xiao Huang, Shao-Jiang Song
Hepatocellular carcinoma (HCC), the most common type of liver cancer, has high morbidity and mortality rates, and its prognosis is poor. The treatment options of HCC are limited by the lack of effective chemotherapy. Therefore, looking for effective drugs with little toxicity is very urgent. The aim of this study was to search for small molecule targeting on liver cancer from Juglans mandshurica, which has been used to treat cancers for a long time in China. Under the guide of anti-hepatoma activity, a new coumarin (1), together with eight reported analogs (2‒9), was isolated from the 75% EtOH extract...
February 19, 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28276509/suppression-of-autophagy-by-mycophenolic-acid-contributes-to-inhibition-of-hcv-replication-in-human-hepatoma-cells
#17
Shoucai Fang, Jinming Su, Bingyu Liang, Xu Li, Yu Li, Junjun Jiang, Jiegang Huang, Bo Zhou, Chuanyi Ning, Jieliang Li, Wenzhe Ho, Yiping Li, Hui Chen, Hao Liang, Li Ye
Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275692/endoplasmic-reticulum-stress-regulates-hepatic-bile-acid-metabolism-in-mice
#18
Anne S Henkel, Brian LeCuyer, Shantel Olivares, Richard M Green
BACKGROUND & AIMS: Cholestasis promotes endoplasmic reticulum (ER) stress in the liver, however, the effect of ER stress on hepatic bile acid metabolism is unknown. We aim to determine the effect of ER stress on hepatic bile acid synthesis and transport in mice. METHODS: ER stress was induced pharmacologically in C57BL/6J mice and human hepatoma (HepG2) cells. The hepatic expression of genes controlling bile acid synthesis and transport was determined. To measure the activity of the primary bile acid synthetic pathway, the concentration of 7α-hydroxy-4-cholesten-3-1 was measured in plasma...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28275194/internal-disequilibria-and-phenotypic-diversification-during-replication-of-hepatitis-c-virus-in-a-non-coevolving-cellular-environment
#19
Elena Moreno, Isabel Gallego, Josep Gregori, Adriana Lucía-Sanz, María Eugenia Soria, Victoria Castro, Nathan M Beach, Susanna C Manrubia, Josep Quer, Juan Ignacio Esteban, Charles M Rice, Jordi Gómez, Pablo Gastaminza, Esteban Domingo, Celia Perales
Viral quasispecies evolution upon long-term virus replication in a non-coevolving cellular environment raises relevant general issues such as the attainment of population equilibrium, compliance with the molecular clock hypothesis or stability of the phenotypic profile. Here we evaluate adaptation, mutant spectrum dynamics, and phenotypic diversification of hepatitis C virus (HCV) in the course of two hundred passages in human hepatoma cells in an experimental design that precluded coevolution of the cells with the virus...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275182/modulation-of-hcv-specific-cd8-effector-t-cell-function-with-antiviral-effect-in-infectious-hepatitis-c-virus-co-culture-model
#20
Keisuke Ojiro, Xiaowang Qu, Hyosun Cho, Jang-June Park, Annelise Vuidepot, Nikolai Lissin, Peter E Molloy, Alan Bennett, Bent K Jakobsen, David E Kaplan, James L Riley, Kyong-Mi Chang
Antiviral effects of hepatitis C virus (HCV)-specific CD8 T-cells have been shown in HCV replicon, but not in authentic infectious cell culture system (HCVcc). Here, we developed tools to examine the antigenicity of HCV-infected HLA A2+ Huh7.5 hepatoma cells (Huh7.5A2) in activating HCV-specific CD8 T-cells with downstream antiviral effects. Infectious HCV epitope mutants encoding well-defined genotype 1a-derived HLA A2-restricted HCV NS3 1073 or NS5 2594 epitope were generated from genotype 2a-derived HCV clone (Jc1Gluc2A) by site-directed mutagenesis...
March 8, 2017: Journal of Virology
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