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https://www.readbyqxmd.com/read/29156767/enhancing-conventional-chemotherapy-drug-cisplatin-induced-anti-tumor-effects-on-human-gastric-cancer-cells-both-in-vitro-and-in-vivo-by-thymoquinone-targeting-pten-gene
#1
Jingjing Ma, Xue Hu, Jiao Li, Dandan Wu, Qingzhi Lan, Qian Wang, Shan Tian, Weiguo Dong
Combination chemotherapy regimen with several anti-tumor drugs is a strategy to improve outcome. Thymoquinone (TQ) has been reported to exert biological activity on various types of human cancers without obvious toxicity. However, only few studies showed the anti-tumor effects of TQ combination with cisplatin on gastric cancer (GC). Here, we showed pretreatment with 5μM TQ significantly increased the apoptotic effects induced by cisplatin on GC cell lines. Combined treatment of cisplatin with TQ represented a significantly superior tumor suppression effect than either agent alone in a xenograft tumor mouse model...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156563/wnt-inhibitory-activity-of-malus-pumila-miller-cv-annurca-and-malus-domestica-cv-limoncella-apple-extracts-on-human-colon-rectal-cells-carrying-familial-adenomatous-polyposis-mutations
#2
Gennaro Riccio, Maria Maisto, Sara Bottone, Nadia Badolati, Giovanni Battista Rossi, Gian Carlo Tenore, Mariano Stornaiuolo, Ettore Novellino
Inhibitors of the Wingless-related Integration site (WNT)/β-catenin pathway have recently been under consideration as potential chemopreventive agents against Familial Adenomatous Polyposis (FAP). This autosomal-dominant syndrome is caused by germline mutations in the gene coding for the protein APC and leads to hyperactivation of the WNT/β-catenin signaling pathway, uncontrolled intestinal cell proliferation and formation of adenocarcinomas. The aim of the present work was to: (i) test, on in vitro cultures of cells carrying FAP mutations and on ex vivo biopsies of FAP patients, the WNT inhibitory activity of extracts from two common southern Italian apples, Malus pumila Miller cv...
November 18, 2017: Nutrients
https://www.readbyqxmd.com/read/29155359/4-methylthio-3-butenyl-isothiocyanate-mediates-nuclear-factor-erythroid-derived-2-like-2-activation-by-regulating-reactive-oxygen-species-production-in-human-esophageal-epithelial-cells
#3
Tadashi Hirata, Young-Man Cho, Isamu Suzuki, Takeshi Toyoda, Jun-Ichi Akagi, Yasushi Nakamura, Satoshi Numazawa, Kumiko Ogawa
4-Methylthio-3-butenyl isothiocyanate (MTBITC) extracted from daikon (Raphanus sativus), which shows antimutagenicity, may have applications as an effective chemopreventive agent in several cancers; however, few reports have described the associated mechanisms. We investigated whether MTBITC induced cytoprotective genes, including phase II enzymes, in Het-1A human esophageal epithelial cells. HMOX1, NQO1, and GCLC mRNA levels and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein levels were increased in Het-1A cells exposed to 10 μM MTBITC...
November 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29154797/caryophyllane-sesquiterpenes-inhibit-dna-damage-by-tobacco-smoke-in-bacterial-and-mammalian-cells
#4
Silvia Di Giacomo, Lorena Abete, Rossana Cocchiola, Gabriela Mazzanti, Margherita Eufemi, Antonella Di Sotto
In the present study, the ability of the natural sesquiterpene β-caryophyllene (CRY) and its metabolite β-caryophyllene oxide (CRYO) to inhibit the genotoxicity of a condensate of cigarette smoke (CSC) was evaluated both in bacterial and mammalian cells. Also, the inhibition of the CSCmediated STAT3 phosphorylation and intracellular oxidative stress was evaluated as potential chemopreventive mechanism. Under our experimental conditions, both the sesquiterpenes exhibited antimutagenic properties, being CRY the most potent compound...
November 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29153737/structure-activity-relationships-and-docking-studies-of-synthetic-2-arylindole-derivatives-determined-with-aromatase-and-quinone-reductase-1
#5
Allan M Prior, Xufen Yu, Eun-Jung Park, Tamara P Kondratyuk, Yan Lin, John M Pezzuto, Dianqing Sun
In our ongoing effort of discovering anticancer and chemopreventive agents, a series of 2-arylindole derivatives were synthesized and evaluated toward aromatase and quinone reductase 1 (QR1). Biological evaluation revealed that several compounds (e.g., 2d, IC50 = 1.61 μM; 21, IC50 = 3.05 μM; and 27, IC50 = 3.34 μM) showed aromatase inhibitory activity with half maximal inhibitory concentration (IC50) values in the low micromolar concentrations. With regard to the QR1 induction activity, 11 exhibited the highest QR1 induction ratio (IR) with a low concentration to double activity (CD) value (IR = 8...
November 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29151594/adipocytes-sustain-pancreatic-cancer-progression-through-a-non-canonical-wnt-paracrine-network-inducing-ror2-nuclear-shuttling
#6
C Carbone, G Piro, N Gaianigo, F Ligorio, R Santoro, V Merz, F Simionato, C Zecchetto, G Falco, G Conti, P T Kamga, M Krampera, F Di Nicolantonio, L De Franceschi, A Scarpa, G Tortora, D Melisi
BACKGROUND: Solid epidemiological evidences connect obesity with incidence, stage, and survival in pancreatic cancer. However, the underlying mechanistic basis linking adipocytes to pancreatic cancer progression remain largely elusive. We hypothesized that factors secreted by adipocytes could be responsible for epithelial-to-mesenchymal transition (EMT) induction and, in turn, a more aggressive phenotype in models of pancreatic preneoplastic lesions. METHODS: We studied the role of factors secreted by two adipogenic model systems from primary human Bone Marrow Stromal Cells (hBMSC) in an in vitro experimental cell transformation model system of human pancreatic ductal epithelial (HPDE) cell stably expressing activated KRAS (HPDE/KRAS),RESULTS:We measured a significant induction of EMT and aggressiveness in HPDE and HPDE/KRAS cell lines when cultured with medium conditioned by fully differentiated adipocytes (ADIPO(CM)) if compared with the same cells cultured with medium conditioned by hBMSC (hBMSC(CM)) from two different healthy donors...
November 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29150967/drug-delivery-strategies-for-chemoprevention-of-uvb%C3%A2-induced-skin-cancer-a-review
#7
REVIEW
Arvind Bagde, Arindam Mondal, Mandip Singh
Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed towards improvements in terms of delivery modes, therapeutic agents and site-specificity of therapeutics delivery...
November 18, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/29149798/reconstructing-biosynthetic-pathway-of-the-plant-derived-cancer-chemopreventive-precursor-glucoraphanin-in-escherichia-coli
#8
Han Yang, Feixia Liu, Yin Li, Bo Yu
Epidemiological data confirmed a strong correlation between regular consumption of cruciferous vegetables and lower cancer risk. This cancer preventive property is mainly attributed to the glucosinolate products, such as glucoraphanin found in broccoli that is derived from methionine. Here we report the first successful reconstruction of the complete biosynthetic pathway of glucoraphanin from methionine in Escherichia coli via gene selection, pathway design, and protein engineering. We used branched-chain amino transferase 3 to catalyze two transamination steps to ensure the purity of precursor molecules and used cysteine as a sulfur donor to simplify the synthesis pathway...
November 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29149616/protective-effects-of-proanthocyanidins-against-cadmium-induced-testicular-injury-through-the-modification-of-nrf2-keap1-signal-path-in-rats
#9
Liu He, Peng Li, Li-Hui Yu, Lin Li, Yi Zhang, Yang Guo, Miao Long, Jian-Bin He, Shu-Hua Yang
The purpose of this study was to evaluate the potential chemoprotective effects of proanthocyanidins (PAs) against cadmium (Cd)-induced oxidative damage of testes via Nrf2-Keap1 signal pathway in rats. Briefly, by using biochemical histological analysis, as well as the real time PCR and western blot approach, oxidative damage in rat testicular tissue was observed after exposure to Cd. In addition, significant down-regulations of mRNA and protein levels of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), γ-glutamyl cysteine synthetase (γ-GCS), glutathione peroxidase (GSH-Px) and quinone oxidoreductase 1 (NQO1), as well as a significant up-regulation of Kelch sample related protein-1 (Keap1) levels in testicular tissue were observed after Cd exposure...
November 3, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#10
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29145169/a-zinc-schiff-base-complex-inhibits-cancer-progression-both-in-vivo-and-in-vitro-by-inducing-apoptosis
#11
Arpita Banerjee, Kaushik Banerjee, Abhinaba Sinha, Satyajit Das, Saikat Majumder, Subrata Majumdar, Soumitra Kumar Choudhuri
Cancer chemotherapy suffers from selectivity and undesired toxicity of the drugs. Since zinc is a biocompatible tracer element and cysteine derivatives are used in cancer chemoprevention, we intend to develop a complex of zinc and cysteine-derivatives as potent, non-toxic anticancer agents. Herein, we synthesized and characterized cysteine based ligand, 2-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-3-mercapto-propionic acid and its Zn-complex, which are found to be non-toxic towards normal human PBMC. Data also revealed that only Zn-complex exhibited remarkable apoptosis in drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cancer cells as assessed by MTT, Cell cycle and AnnexinV binding assay...
November 6, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29144773/cancer-chemopreventive-antiproliferative-and-superoxide-anion-scavenging-properties-of-kluyveromyces-marxianus-and-saccharomyces-cerevisiae-var-boulardii-cell-wall-components
#12
Olivier Fortin, Blanca Aguilar-Uscanga, Khanh Dang Vu, Stephane Salmieri, Monique Lacroix
This study investigated the cancer chemopreventive, the antiradical, and the antiproliferative properties of polysaccharides extracts from cell wall of Saccharomyces boulardii and Kluyveromyces marxianus. β-glucan, mannan, and chitin were also quantified to identify the most important extract responsible for these biological properties. Soluble and insoluble glucans as well as mannoprotein were extracted from cell wall using single hot-alkaline method. Superoxide anion scavenging (antiradical capacity), NAD(P)H: quinone reductase (QR) (EC 1...
November 16, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29144397/sulforaphane-alters-%C3%AE-naphthoflavone-induced-changes-in-activity-and-expression-of-drug-metabolizing-enzymes-in-rat-hepatocytes
#13
Kateřina Lněničková, Andrea Dymáková, Barbora Szotáková, Iva Boušová
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but little is known about the effect of SFN in combination with cytochrome P450 (CYP) inducer. The aim of our study was to evaluate the effect of SFN on the activity and gene expression of selected DMEs in primary cultures of rat hepatocytes treated or non-treated with β-naphthoflavone (BNF), the model CYP1A inducer...
November 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29141545/main-isoflavones-found-in-dietary-sources-as-natural-anti-inflammatory-agents
#14
Corina Danciu, Stefana Avram, Ioana Pavel, Roxana Ghiulai, Cristina Dehelean, Alexa Ersilia, Daliana Minda, Cristina Petrescu, Elena Moaca, Codruta Soica
BACKGROUND: Isoflavones are natural compounds belonging to the class of isoflavonoids, molecules with a chemical structure based on the 3-phenyl chromen-4-one backbone. As a particular element, the isoflavones are called also phytoestrogens, due to the structural similarity with 17-β estradiol, the primary female sex hormone, presenting both estrogen-agonist and estrogen-antagonist properties. This class of secondary plant metabolites has been extensively reported in the literature for a wide range of therapeutic activities including antioxidant, chemopreventive, anti-inflammatory, anti-allergic, antibacterial, cardio preventive effects...
November 9, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29141455/methionine-adenosyltransferases-in-cancers-mechanisms-of-dysregulation-and-implications-for-therapy
#15
Lauren Y Maldonado, Diana Arsene, José M Mato, Shelly C Lu
Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes - MAT1A, MAT2A, and MAT2B - with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29138815/curcumin-reverses-tobacco-smoke%C3%A2-induced-epithelial%C3%A2-mesenchymal-transition-by-suppressing-the-mapk-pathway-in-the-lungs-of-mice
#16
Zhaofeng Liang, Rui Wu, Wei Xie, Mingming Zhu, Chunfeng Xie, Xiaoting Li, Jianyun Zhu, Weiwei Zhu, Jieshu Wu, Shanshan Geng, Wenrong Xu, Caiyun Zhong, Hongyu Han
Tobacco smoke is a major risk factor for lung cancer. Epithelial‑mesenchymal transition (EMT) is decisive in cancer invasion and metastasis, and therefore promotes cancer progression. Mitogen‑activated protein kinase (MAPK) pathways are implicated in various aspects of cancer development and progression, including the EMT process. The chemopreventive effect of curcumin on carcinogenesis has been reported in vivo and in vitro. The present study investigated tobacco smoke‑induced alterations in the MAPK/activator protein‑1 (AP‑1) pathways, and pulmonary EMT changes in the lungs of mice, and further observed the chemopreventive effect of curcumin...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138024/-e-3-3-4-5-trimethoxyphenyl-1-pyridin-4-yl-prop-2-en-1-one-a-heterocyclic-chalcone-is-a-potent-and-selective-cyp1a1-inhibitor-and-cancer-chemopreventive-agent
#17
Neill J Horley, Kenneth J M Beresford, Supriya Kaduskar, Prashant Joshi, Glen J P McCann, Ketan C Ruparelia, Ibidapo S Williams, Linda Gatchie, Vinay R Sonawane, Sandip B Bharate, Bhabatosh Chaudhuri
The overexpression of CYP1 family of enzymes is reported to be associated with development of human carcinomas. It has been well reported that CYP1A1 specific inhibitors prevents carcinogenesis. Herein, thirteen pyridine-4-yl series of chalcones were synthesized and screened for inhibition of CYP1 isoforms 1A1, 1B1 and 1A2 in Sacchrosomes™ and live human HEK293 cells. The structure-activity relationship analysis indicated that chalcones bearing tri-alkoxy groups (8a and 8k) on non-heterocyclic ring displayed selective inhibition of CYP1A1 enzyme, with IC50 values of 58 and 65 nM, respectively...
November 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29137257/kaempferol-induces-hepatocellular-carcinoma-cell-death-via-endoplasmic-reticulum-stress-chop-autophagy-signaling-pathway
#18
Haiqing Guo, Wei Lin, Xiangying Zhang, Xiaohui Zhang, Zhongjie Hu, Liying Li, Zhongping Duan, Jing Zhang, Feng Ren
Kaempferol is a flavonoid compound that has gained widespread attention due to its antitumor functions. However, the underlying mechanisms are still not clear. The present study investigated the effect of kaempferol on hepatocellular carcinoma and its underlying mechanisms. Kaempferol induced autophagy in a concentration- and time-dependent manner in HepG2 or Huh7 cells, which was evidenced by the significant increase of autophagy-related genes. Inhibition of autophagy pathway, through 3-methyladenine or Atg7 siRNA, strongly diminished kaempferol-induced apoptosis...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136951/chemopreventive-effect-of-myricetin-a-natural-occurring-compound-on-colonic-chronic-inflammation-and-inflammation-driven-tumorigenesis-in-mice
#19
Mei-Jia Zhang, Han Su, Jing-Yue Yan, Na Li, Zhi-Yu Song, Huai-Jie Wang, Lian-Guang Huo, Feng Wang, Wan-Sheng Ji, Xian-Jun Qu, Mei-Hua Qu
Myricetin is a flavonoids compound extracted from edible myrica rubra. We aimed to evaluate the efficacy of Myricetin on colonic chronic inflammation and inflammation-driven tumorigenesis in mice. Myricetin was administrated by gavage for 4 consecutive weeks. Mice were sacrificed and the number of colonic polyps was counted. Myricetin significantly inhibited AOM/DSS-induced colitis and colorectal tumorigenesis. Myricetin prevented the incidence of colorectal tumorigenesis and reduced the size of colorectal polyps...
November 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29134640/reduced-il-6-levels-and-tumor-associated-phospho-stat3-are-associated-with-reduced-tumor-development-in-a-mouse-model-of-lung-cancer-chemoprevention-with-myo-inositol
#20
Nese Unver, Oliver Delgado, Kirubel Zeleke, Amber Cumpian, Ximing Tang, Mauricio S Caetano, Hong Wang, Hiroyuki Katayama, Hua Yu, Eva Szabo, Ignacio Wistuba, Seyed Javad Moghaddam, Samir Hanash, Edwin J Ostrin
Several promising chemopreventive agents have for lung cancer emerged in preclinical models and in retrospective trials. These agents have been shown to modulate pathways altered in carcinogenesis and reduce markers of carcinogenesis in animal and cell culture models. Cancer-prone transgenic mice with oncogenic Kras expressed in the airway epithelium (Ccsp(Cre/+) ; Kras(LSL-G12D/+) ) were raised on diets compounded with myo-inositol. These animals form lung premalignant lesions in a stereotypical fashion over the ten weeks following weaning...
November 14, 2017: International Journal of Cancer. Journal International du Cancer
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