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https://www.readbyqxmd.com/read/29232580/design-and-synthesis-of-novel-quinacrine-1-3-thiazinan-4-one-hybrids-for-their-anti-breast-cancer-activity
#1
V Raja Solomon, Sheetal Pundir, Hoang-Thanh Le, Hoyun Lee
In an attempt to develop effective and safe anticancer agents, we designed, synthesized and examined 23 novel quinacrine (QC) derivatives by combining the 9-aminoacridine scaffold and the [1,3]thiazinan-4-ones group. Most of these hybrids showed strong anticancer activities, among which 3-(3-(6-chloro-2-methoxyacridin-9-ylamino)propyl)-2-(thiophen-2-yl)-1,3-thiazinan-4-one (25; VR151) effectively killed many different cancer cell types, including eight breast cancer cell lines with different genetic background, two prostate cancer and two lung cancer cell lines...
December 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29214461/co-ingestion-of-protein-or-a-protein-hydrolysate-with-carbohydrate-enhances-anabolic-signaling-but-not-glycogen-resynthesis-following-recovery-from-prolonged-aerobic-exercise-in-trained-cyclists
#2
Karl E Cogan, Mark Evans, Enzo Iuliano, Audrey Melvin, Davide Susta, Karl Neff, Giuseppe De Vito, Brendan Egan
PURPOSE: The effect of carbohydrate (CHO), or CHO supplemented with either sodium caseinate protein (CHO-C) or a sodium caseinate protein hydrolysate (CHO-H) on the recovery of skeletal muscle glycogen and anabolic signaling following prolonged aerobic exercise was determined in trained male cyclists [n = 11, mean ± SEM age 28.8 ± 2.3 years; body mass (BM) 75.0 ± 2.3 kg; VO2peak 61.3 ± 1.6 ml kg-1 min-1]. METHODS: On three separate occasions, participants cycled for 2 h at ~ 70% VO2peak followed by a 4-h recovery period...
December 6, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/29212844/protein-synthesis-is-lowered-by-4ebp1-and-eif2-%C3%AE-signaling-while-protein-degradation-may-be-maintained-in-fasting-hypoxic-amazonian-cichlid-astronotus-ocellatus
#3
A A Cassidy, W R Driedzic, D Campos, W Heinrichs-Caldas, V M F Almeida-Val, A L Val, S G Lamarre
The Amazonian cichlid, Astronotus ocellatus, is highly tolerant to hypoxia, and is known to reduce its metabolic rate by reducing the activity of energetically expensive metabolic processes when oxygen is lacking in their environment. Our objectives were to determine how protein metabolism is regulated in A. ocellatus during hypoxia. Fish were exposed to a stepwise decrease in air saturation (100%, 20%, 10% and 5%) for 2 hours at each level, and sampled throughout the experiment. A flooding dose technique using a stable isotope allowed us to observe an overall decrease in protein synthesis during hypoxia in liver, muscle, gill and heart...
December 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29204055/combined-treatment-of-pancreatic-cancer-xenograft-with-90y-itga6b4-mediated-radioimmunotherapy-and-pi3k-mtor-inhibitor
#4
Winn Aung, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Yoshinori Ukai, Katsushi Kouda, Yoshikazu Kurosawa, Takako Furukawa, Tsuneo Saga, Tatsuya Higashi
AIM: To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy (RIT) and PI3K/mTOR inhibitor BEZ235 in a pancreatic cancer model. METHODS: Phosphorylation of Akt, mTOR, the downstream effectors eukaryotic initiation factor 4E binding protein 1 (4EBP1) and S6 ribosomal protein (S6) were evaluated in BxPC-3 human pancreatic cancer cells treated with Yttrium-90 (90Y) labeled anti-integrin α6β4 antibody (ITGA6B4) and BEZ235 by western blotting...
November 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29198077/fibroblast-like-synoviocyte-migration-is-enhanced-by-il-17-mediated-overexpression-of-l-type-amino-acid-transporter-1-lat1-via-the-mtor-4e-bp1-pathway
#5
Zhao Yu, Wang Lin, Zhang Rui, Pan Jihong
In rheumatoid arthritis (RA), activated synovial fibroblasts have the ability to invade joint cartilage, actively contributing to joint destruction in RA. The mechanisms underlying this cell migration and invasion remain unclear. Our previous results and data from the GEO profile indicate that the L-type amino acid transporter gene, LAT1, is overexpressed in the synovium of RA. To identify its potential role in RA, fibroblast-like synoviocytes (FLS) from patients with RA were used to determine the effects of suppressing the LAT1 genes using RNA interference and the LAT inhibitor, BCH...
December 2, 2017: Amino Acids
https://www.readbyqxmd.com/read/29182407/metformin-is-associated-with-reduced-cell-proliferation-in-human-endometrial-cancer-by-inbibiting-pi3k-akt-mtor-signaling
#6
Yan Zhao, Hongli Sun, Minjuan Feng, Jinyan Zhao, Xiaogui Zhao, Qiuyuan Wan, Dongge Cai
Metformin recently gained traction as potential anti-endometrial cancer agent for its new applications. However, the underlying mechanisms of the anti-cancer effect of metformin in the endometrial cancer have not yet been fully elucidated. Sixty-five patients diagnosed as endometrial carcinoma were grouped into (n = 33) and non-treatment mixed (n = 32) for analysis. Thirty healthy donors were recruited as controls. We attempt to investigate the effect of metformin on Ki-67, PI3K, p-AKT, p-S6K1, and p-4EBP1 staining in human endometrial cancer by immunohistochemical staining...
November 28, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29167573/metformin-transiently-inhibits-colorectal-cancer-cell-proliferation-as-a-result-of-either-ampk-activation-or-increased-ros-production
#7
Angela Mogavero, Maria Valeria Maiorana, Susanna Zanutto, Luca Varinelli, Fabio Bozzi, Antonino Belfiore, Chiara C Volpi, Annunziata Gloghini, Marco A Pierotti, Manuela Gariboldi
Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce cancer risk and improve the prognosis of certain malignancies. However, the mechanism underlying its anti-cancer effect is still unclear. We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin reduced cell proliferation and migration by inducing cell cycle arrest in the G0/G1 phase. This was accompanied by a sharp decrease in the expression of c-Myc and down-regulation of IGF1R...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146112/different-concentrations-of-docosahexanoic-acid-supplement-during-lactation-result-in-different-outcomes-in-preterm-sprague-dawley-rats
#8
Qian Wang, Chunhong Jia, Xiaohua Tan, Fan Wu, Xinqi Zhong, Zhiwen Su, Weiwen Sun, Qiliang Cui
PROPOSE: In this study, we evaluated the effects of different concentrations of docosahexanoic acid (DHA) supplement on preterm Sprague-Dawley rat pups, and in parallel, measured the phosphorylation activity of the mTOR pathway in the hippocampal CA1 area. METHODS: Preterm Sprague-Dawley rat pups were randomly assigned to experimental groups which included; a sufficient DHA group (100 mg/kg/day); an enriched DHA group (300 mg/kg/day); an excess DHA group (800 mg/kg/day); and a deficient DHA group (normal saline gavage 0...
November 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29128353/pyruvate-dehydrogenase-kinase-4-mediates-lipogenesis-and-contributes-to-the-pathogenesis-of-nonalcoholic-steatohepatitis
#9
Ming Zhang, Yujie Zhao, Zhen Li, Congying Wang
Nonalcoholic steatohepatitis (NASH) is a progressive disease and poses a high risk of severe liver damage. However, the pathogenesis of NASH is still unclear. Accumulation of lipid droplets and insulin resistance is the hallmark of NASH. Pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) plays key role in glucose metabolism via regulating the activity of pyruvate dehydrogenase complex (PDC). Here, we demonstrated a novel of PDK4 in NASH by regulating hepatic steatosis and insulin signaling pathway in methionine and choline deficient (MCD) diet induced NASH model...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29115478/torin2-enhances-the-radiosensitivity-of-mcf%C3%A2-7-breast-cancer-cells-by-downregulating-the-mtor-signaling-pathway-and-atm-phosphorylation
#10
Jia Luo, Guocheng Pi, He Xiao, Yunfei Ye, Qing Li, Lianhua Zhao, Huan Huang, Hong Luo, Qin Zhang, Dong Wang, Ge Wang
Radiotherapy has an important role in the comprehensive treatment of breast cancer. However, the clinical outcome of adjuvant radiotherapy may be limited due to intrinsic radioresistance, it is necessary to explore efficient radiosensitization methods that improve the clinical outcome of patients undergoing radiotherapy. The present study aimed to investigate whether the novel mechanistic target of rapamycin (mTOR) inhibitor Torin2 enhances the radiosensitivity of MCF‑7 breast cancer cells. A Cell Counting Kit‑8 (CCK‑8) assay was performed to measure the effect of Torin2 on cell proliferation, while clonogenic assays were employed to determine the effect of Torin2 in combination with radiation on the proliferation of MCF‑7 cells...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29103956/mtorc1-mediated-inhibition-of-4ebp1-is-essential-for-hedgehog-signaling-driven-translation-and-medulloblastoma
#11
Chang-Chih Wu, Shirui Hou, Brent A Orr, Bryan R Kuo, Yong Ha Youn, Taren Ong, Fanny Roth, Charles G Eberhart, Giles W Robinson, David J Solecki, Makoto M Taketo, Richard J Gilbertson, Martine F Roussel, Young-Goo Han
Mechanistic target of rapamycin (MTOR) cooperates with Hedgehog (HH) signaling, but the underlying mechanisms are incompletely understood. Here we provide genetic, biochemical, and pharmacologic evidence that MTOR complex 1 (mTORC1)-dependent translation is a prerequisite for HH signaling. The genetic loss of mTORC1 function inhibited HH signaling-driven growth of the cerebellum and medulloblastoma. Inhibiting translation or mTORC1 blocked HH signaling. Depleting 4EBP1, an mTORC1 target that inhibits translation, alleviated the dependence of HH signaling on mTORC1...
October 31, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29093267/loss-of-mir-141-200c-ameliorates-hepatic-steatosis-and-inflammation-by-reprogramming-multiple-signaling-pathways-in-nash
#12
Melanie Tran, Sang-Min Lee, Dong-Ju Shin, Li Wang
Accumulation of lipid droplets and inflammatory cell infiltration is the hallmark of nonalcoholic steatohepatitis (NASH). The roles of noncoding RNAs in NASH are less known. We aim to elucidate the function of miR-141/200c in diet-induced NASH. WT and miR-141/200c-/- mice were fed a methionine and choline deficient (MCD) diet for 2 weeks to assess markers of steatosis, liver injury, and inflammation. Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29081412/mir-101-reduces-cell-proliferation-and-invasion-and-enhances-apoptosis-in-endometrial-cancer-via-regulating-pi3k-akt-mtor
#13
Suxia Zhang, Min Wang, Qirong Li, Ping Zhu
PI3K/Akt/mTOR signaling pathway plays an important role in tumor development. mTOR overexpression and PI3K/ Akt/mTOR signaling pathway enhancement were found in endometrial cancer (EC). MiR-101 was found downregulated in EC. Bioinformatics analysis showed the binding site between miR-101 and the 3'-UTR of mTOR mRNA. This study investigated the role of miR-101 in affecting EC proliferation, apoptosis, and invasion, and mediating mTOR expression. EC tumor tissue and normal endometrial tissue were collected from Jinan maternity and child care hospital...
October 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29069736/a-novel-synthetic-derivative-of-quercetin-8-trifluoromethyl-3-5-7-3-4-o-pentamethyl-quercetin-inhibits-bladder-cancer-growth-by-targeting-the-ampk-mtor-signaling-pathway
#14
Ting Tao, Caimei He, Jun Deng, Yanjun Huang, Qiongli Su, Mei Peng, Meiling Yi, Kwame Oteng Darko, Hui Zou, Xiaoping Yang
Quercetin is a naturally existing compound and shows attractive anticancer properties for a variety of solid tumors including glioma, bladder cancer, hepatocellular carcinoma, breast cancer, hematological malignancies and prostate carcinoma. However, these anticancer properties have not been clinically approved due to unclear mechanistic information and its low bioactivity. In our previous study, we elucidated that quercetin activates AMPK pathway which is the major mechanism for its unique anticancer effect in bladder cancer...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28984836/balanced-diet-fed-fat-1-transgenic-mice-exhibit-lower-hindlimb-suspension-induced-soleus-muscle-atrophy
#15
Gabriel Nasri Marzuca-Nassr, Gilson Masahiro Murata, Amanda Roque Martins, Kaio Fernando Vitzel, Amanda Rabello Crisma, Rosângela Pavan Torres, Jorge Mancini-Filho, Jing Xuan Kang, Rui Curi
The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle...
October 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28965934/the-activation-of-autophagy-protects-neurons-and-astrocytes-against-bilirubin-induced-cytotoxicity
#16
Mohammed Qaisiya, Paula Mardešić, Beatrice Pastore, Claudio Tiribelli, Cristina Bellarosa
Unconjugated bilirubin (UCB) neurotoxicity involves oxidative stress, calcium signaling and ER-stress. The same insults can also induce autophagy, a process of "self-eating", with both a pro-survival or a pro-apoptotic role. Our aim was to study the outcome of autophagy activation by UCB in the highly sensitive neuronal SH-SY5Y cells and in the resistant astrocytoma U87 cells. Upon treatment with a toxic dose of UCB, the conversion of LC3-I to LC3-II was detected in both cell lines. Inhibition of autophagy by E64d before UCB treatment increased SH-SY5Y cell mortality and made U87 cells sensitive to UCB...
November 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28962554/propofol-enhances-bcr-abl-tkis-inhibitory-effects-in-chronic-myeloid-leukemia-through-akt-mtor-suppression
#17
Zhimin Tan, Aixia Peng, Jingwen Xu, Mingwen Ouyang
BACKGROUND: The anti-cancer activities of intravenous anesthetic drug propofol have been demonstrated in various types of cancers but not in chronic myeloid leukemia (CML). METHODS: We systematically examined the effect of propofol and its combination with BCR-ABL tyrosine kinase inhibitors (TKIs) in CML cell lines, patient progenitor cells and mouse xenograft model. We analyzed propofol's underlying mechanism focusing on survival pathway in CML cells. RESULTS: We show that propofol alone is active in inhibiting proliferation and inducing apoptosis in KBM-7, KU812 and K562 cells, and acts synergistically with imatinib or dasatinib, in in vitro cell culture system and in vivo xenograft model...
September 29, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28961193/fascaplysin-exerts-anti-cancer-effects-through-the-downregulation-of-survivin-and-hif-1%C3%AE-and-inhibition-of-vegfr2-and-trka
#18
Taek-In Oh, Yoon-Mi Lee, Taek-Jin Nam, Young-San Ko, Shinmee Mah, Jinhee Kim, Younghoon Kim, Rallabandi Harikrishna Reddy, Young Jun Kim, Sungwoo Hong, Ji-Hong Lim
Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4); however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB), indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues...
September 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28939765/thioredoxin-1-maintains-mtor-function-during-oxidative-stress-in-cardiomyocytes
#19
Shin-Ichi Oka, Tsuyoshi Hirata, Wataru Suzuki, Daichi Naito, Yanbin Chen, Adave Chin, Hiroaki Yaginuma, Toshiro Saito, Narayani Nagarajan, Peiyong Zhai, Santosh Bhat, Kevin Schesing, Dan Shao, Yoko Hirabayashi, Junji Yodoi, Sebastiano Sciarretta, Junichi Sadoshima
Thioredoxin 1 (Trx1) is a 12 kDa oxidoreductase that catalyzes thiol-disulfide exchange reactions to reduce proteins with disulfide bonds. As such, Trx1 helps protect the heart against stresses, such as ischemia and pressure overload. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, metabolism and survival. We have previously shown that mTOR activity is increased in response to myocardial ischemia-reperfusion injury. However, whether Trx1 interacts with mTOR to preserve heart function remains unknown...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28927274/fluoride-induced-autophagy-via-the-regulation-of-phosphorylation-of-mammalian-targets-of-rapamycin-in-mice-leydig-cells
#20
Jianhai Zhang, Yuchen Zhu, Yan Shi, Yongli Han, Chen Liang, Zhiyuan Feng, Heping Zheng, Michelle Eng, Jundong Wang
Fluoride is known to impair testicular function and decrease testosterone levels, yet the underlying mechanisms remain inconclusive. The objective of this study is to investigate the roles of autophagy in fluoride-induced male reproductive toxicity using both in vivo and in vitro Leydig cell models. Using transmission electron microscopy and monodansylcadaverine staining, we observed increasing numbers of autophagosomes in testicular tissue, especially in Leydig cells of fluoride-exposed mice. Further study revealed that fluoride increased the levels of mRNA and protein expression of autophagy markers LC3, Beclin1, and Atg 5 in primary Leydig cells...
October 11, 2017: Journal of Agricultural and Food Chemistry
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