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https://www.readbyqxmd.com/read/29147649/knockdown-of-sirt1-suppresses-bladder-cancer-cell-proliferation-and-migration-and-induces-cell-cycle-arrest-and-antioxidant-response-through-foxo3a-mediated-pathways
#1
Qingxuan Hu, Gang Wang, Jianping Peng, Guofeng Qian, Wei Jiang, Conghua Xie, Yu Xiao, Xinghuan Wang
Bladder cancer (BCa) is one of the most common tumors, but its underlying mechanism has not been fully clarified. Our transcriptome analysis suggested a close link of Sirtuins, Peroxisome Proliferator-Activated Receptor (PPAR), cell cycle regulation, reactive oxygen species (ROS) metabolism, and Forkhead Box Class O (FOXO) signaling pathway in BCa. SIRT1 is a key member of Sirtuins, playing important roles in aging and energy metabolism, which has been reported to be involved in various metabolic diseases and tumors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29141862/the-activation-of-human-dermal-microvascular-cells-by-poly-i-c-lipopolysaccharide-imiquimod-and-odn2395-is-mediated-by-the-fli1-foxo3a-pathway
#2
Lukasz Stawski, Grace Marden, Maria Trojanowska
Endothelial cell (EC) dysfunction has been associated with inflammatory and autoimmune diseases; however, the factors contributing to this dysfunction have not been fully explored. Because activation of TLRs has been implicated in autoimmune diseases, the goal of this study was to determine the effects of TLR ligands on EC function. Human dermal microvascular ECs (HDMECs) treated with TLR3 [Poly(I:C)], TLR4 (LPS), and TLR7 (imiquimod) agonists showed decreased proliferation and a reduced total number of branching tubules in three-dimensional human dermal organoid ex vivo culture...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29137323/nvp-bkm120-inhibits-colon-cancer-growth-via-foxo3a-dependent-puma-induction
#3
Shida Yang, Xin Li, Wenchang Guan, Mingqin Qian, Zhicheng Yao, Xiaoxue Yin, Hongmei Zhao
NVP-BKM120, a potent and highly selective PI3K inhibitor, is currently being investigated in phase I/II clinical trials. The mechanisms of action of NVP-BKM120 in colon cancer cells are unclear. In the present study, we investigated how NVP-BKM120 suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. We found that NVP-BKM120 treatment enhance PUMA induction irrespective of p53 status through the FoxO3a pathway following AKT inhibition. Furthermore, PUMA is required for NVP-BKM120-induced apoptosis in colon cancer cells...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131261/mir-96-expression-in-prostate-cancer-and-its-effect-on-the-target-gene-regulation
#4
Y-H Bao, Y Wang, Y Liu, S Wang, B Wu
OBJECTIVE: Previous studies showed that miR-96 was associated with a carcinogenic effect. To investigate the expression of miR-96 and related target genes in the regulation of prostatic cancer, we compared the expression of miR-96 in both prostatic cancer and adjacent normal tissues, and explored the role of miR-96 in prostate cancer. PATIENTS AND METHODS: PC-3 cell line originated from human prostatic cancer tissues was prepared. RNA was extracted for examination of miR-96 expression...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29130614/panax-notoginseng-saponins-attenuate-cardiomyocyte-apoptosis-through-mitochondrial-pathway-in-natural-aging-rats
#5
Zhiyong Zhou, Jiao Wang, Yanan Song, Yumin He, Changcheng Zhang, Chaoqi Liu, Haixia Zhao, Yaoyan Dun, Ding Yuan, Ting Wang
Panax notoginseng saponins (PNS) have been widely used in the cardiovascular system for the treatment of cardiovascular diseases and stroke in China. In this study, we investigated the anti-apoptotic effect of PNS on cardiomyocytes in the natural aging rat and explored the potential mechanisms regarding oxidative stress and mitochondrial function signaling pathways. Male Sprague-Dawley rats were randomly divided into five groups: adult control (3-month old), aging control (24-month old), and different doses of PNS-treated aging rat groups (10, 30, 60 mg/kg/day, orally)...
November 12, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29124072/decitabine-induced-changes-in-human-myelodysplastic-syndrome-cell-line-skm-1-are-mediated-by-foxo3a-activation
#6
Wen Zeng, Hanjun Dai, Ming Yan, Xiaojun Cai, Hong Luo, Min Ke, Zeming Liu
The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes. We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29119376/regulatory-effects-of-antitumor-agent-matrine-on-foxo-and-pi3k-akt-pathway-in-castration-resistant-prostate-cancer-cells
#7
Qi Li, Hai Huang, Zheng He, Yi Sun, Yufeng Tang, Xiaohong Shang, Chengbin Wang
We previously demonstrated that matrine could inhibit the proliferating, migrating, as well as invading processes of both PC-3 and DU145 cells. However, the underlying molecular mechanisms have not yet been clearly defined. In this study, using various techniques such as high throughput sequencing technology, bioinformatics, quantitative real-time PCR, and immunoblot analysis, we aimed to understand whether matrine serves as a novel regulator of FOXO and PI3K-AKT signaling pathway. DU145 and PC-3 cell lines were cultured for 24 h in vitro...
November 7, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29115437/simvastatin-enhances-the-radiosensitivity-of-p53%C3%A2-deficient-cells-via-inhibition-of-mouse-double-minute-2-homolog
#8
Ji Young Lee, Mi-Sook Kim, Jae Eun Ju, Mi So Lee, Namhyun Chung, Youn Kyoung Jeong
Simvastatin exhibits anticancer activities, but its molecular mechanisms and radiosensitizing effects relative to p53 status remain unclear. In this study, we investigated whether the combination of simvastatin and ionizing radiation (IR) would enhance the antitumor effects of IR alone in HCT116 p53+/+ and p53‑/- colon cancer cells. Using colony formation assays and a xenograft mouse model, we found that simvastatin potently stimulated radiosensitization of HCT116 p53‑/- cells and xenograft tumors. The combination of simvastatin with IR decreased G2/M arrest and delayed the repair of IR-induced DNA damage; however, no differences between the HCT116 p53+/+ and p53‑/- cells were evident...
November 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29113252/microrna-25-contributes-to-cisplatin-resistance-in-gastric-cancer-cells-by-inhibiting-forkhead-box-o3a
#9
Jingbo He, Huixiong Qi, Fang Chen, Chuanhua Cao
Gastric cancer (GC) is a common type of malignancy worldwide, and chemotherapeutic resistance accounts for the majority of the failures in clinical treatment. MicroRNAs (miRs) are a class of small non-coding RNAs, which serve essential roles in GC. The present study aimed to investigate the potential role of miR-25 in the cisplatin sensitivity of GC cells. The expression level of miR-25 was significantly upregulated in the cisplatin-resistant GC cell line SGC-7901/DDP compared with the SGC-7901 parental cell line...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29100348/changes-of-foxo3a-in-pbmcs-and-its-associations-with-stress-hyperglycemia-in-acute-obstructive-suppurative-cholangitis-patients
#10
Niu Bailin, Chen Nan, Li Peizhi, He Kun, Zhu Xiwen, Ren Guosheng, Gong Jianping, Zhang Wenfeng
Objective: The levels of Foxo3a in the peripheral blood mononuclears cells (PBMCs) before and after treatment were detected in acute obstructive suppurative cholangitis (AOSC) patients to evaluate the associations between Foxo3a and stress hyperglycemia (SHG). Methods: PBMCs were obtained from AOSC patients (n=28) on admission (AP), from patients at 1 week after cure (RP) and from healthy volunteers (HV) (n=14) to evaluate the relationship between the protein levels of Foxo3a and the serum levels of glucose...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081748/coq10-augments-rosuvastatin-neuroprotective-effect-in-a-model-of-global-ischemia-via-inhibition-of-nf-%C3%AE%C2%BAb-jnk3-bax-and-activation-of-akt-foxo3a-bim-cues
#11
Sarah A Abd El-Aal, Mai A Abd El-Fattah, Hanan S El-Abhar
Statins were reported to lower the Coenzyme Q10 (CoQ10) content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg), CoQ10 (10 mg/kg) and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29080747/trip6-promotes-cell-proliferation-in-hepatocellular-carcinoma-via-suppression-of-foxo3a
#12
Wenhui Zhao, Yubin Dai, Ting Dai, Tian Xie, Xiaobo Su, Jing Li, Xiang Zhou, Kewei Meng, Xiaohui Zhao
Thyroid hormone receptor-interacting protein 6 (TRIP6), a member of LIM family, acts as an adaptor protein and is overexpressed in several tumor types. However, the clinical significance and biological role of TRIP6 in HCC remains unknown. In our study, we found that TRIP6 was markedly overexpressed in HCC cells and clinical specimens compared with normal hepatocytes and adjacent non-tumor tissues. Immunohistochemical and statistical analysis showed that the expression of TRIP6 significantly correlated with HCC patients' clinical stage and poor survival...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29079711/histone-deacetylase-inhibition-enhances-the-antitumor-activity-of-a-mek-inhibitor-in-lung-cancer-cells-harboring-ras-mutations
#13
Tadaaki Yamada, Joseph M Amann, Azusa Tanimoto, Hirokazu Taniguchi, Takehito Shukuya, Cynthia Timmers, Seiji Yano, Konstantin Shilo, David P Carbone
Non-small-cell lung cancer (NSCLC) can be identified by precise molecular subsets based on genomic alterations that drive tumorigenesis and include mutations in EGFR, KRAS, and various ALK fusions. However, despite effective treatments for EGFR and ALK, promising therapeutics have not been developed for patients with KRAS mutations. It has been reported that one way the RAS-ERK pathway contributes to tumorigenesis is by affecting stability and localization of FOXO3a protein, an important regulator of cell death and the cell cycle...
October 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29073599/combination-of-solamargine-and-metformin-strengthens-igfbp1-gene-expression-through-inactivation-of-stat3-and-reciprocal-interaction-between-foxo3a-and-sp1
#14
Qing Tang, Fang Zheng, JingJing Wu, Qian Xiao, Liuning Li, Swei Sunny Hann
BACKGROUND/AIMS: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE2) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined...
October 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29054856/levels-of-%C3%AE-and-%C3%AE-synuclein-regulate-cellular-susceptibility-to-toxicity-from-%C3%AE-synuclein-oligomers
#15
Dafina M Angelova, Hannah B L Jones, David R Brown
α-Synuclein (α-syn) is associated with a range of diseases, including Parkinson disease. In disease, α-syn is known to aggregate and has the potential to be neurotoxic. The association between copper and α-syn results in the formation of stellate toxic oligomers that are highly toxic to cultured neurons. We further investigated the mechanism of toxicity of α-syn oligomers. Cells that overexpress α-syn showed increased susceptibility to the toxicity of the oligomers, while those that overexpressed β-syn showed increased resistance to the toxic oligomers...
October 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29046298/identification-of-dual-mechanisms-mediating-5-hydroxytryptamine-receptor-1f-induced-mitochondrial-biogenesis
#16
Whitney S Gibbs, Sara M Garrett, Craig C Beeson, Rick G Schnellmann
Our laboratory recently made the novel observation that 5-hydroxytryptamine 1F (5-HT1F) receptor activation induces mitochondrial biogenesis (MB), the production of new, functional mitochondria, in vitro and vivo. We sought to determine the mechanism linking the 5-HT1F receptor to MB in renal proximal tubule cells. Using LY344864, a selective 5-HT1F receptor agonist, we determined that the 5-HT1F receptor is coupled to Gαi/o and induces MB through Gβγ dependent activation of Akt, endothelial nitric oxide (eNOS), cyclic guanosine-monophosphate (cGMP), protein kinase G (PKG) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)...
October 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29044520/quercetin-protects-against-radiocontrast-medium-toxicity-in-human-renal-proximal-tubular-cells
#17
Michele Andreucci, Teresa Faga, Antonio Pisani, Raffele Serra, Domenico Russo, GIovambattista De Sarro, Ashour Michael
Radiocontrast media (RCM)-induced acute kidney injury (CI-AKI) is a major clinical problem whose, pathophysiology is not well understood. Direct toxic effects on renal cells, possibly mediated by reactive oxygen species, have been postulated as contributing to CI-AKI. We investigated the effect of quercetin on human renal proximal tubular (HK-2) cells treated with the radiocontrast medium (RCM) sodium diatrizoate. Quercetin is the most widely studied flavonoid, and the most abundant flavonol present in foods...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29030976/synergistic-effect-of-hif-1%C3%AE-and-foxo3a-trigger-cardiomyocyte-apoptosis-under-hyperglycemic-ischemia-condition
#18
Ya-Fang Chen, Sudhir Pandey, Cecilia Hsuan Day, Yu-Feng Chen, Ai-Zhi Jiang, Tsung-Jung Ho, Ray-Jade Chen, Vijaya PadmaViswanadha, Wei-Wen Kuo, Chih-Yang Huang
Cardiomyocyte death is an important pathogenic feature of ischemia and heart failure. Through this study, we showed the synergistic role of HIF-1α and FoxO3a in cardiomyocyte apoptosis subjected to hypoxia plus elevated glucose levels. Using gene specific small interfering RNAs (siRNA), semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), western blot, immunofluorescence, nuclear and cytosolic localization and TUNEL assay techniques, we determined that combined function of HIF-1α and FoxO3a under high glucose plus hypoxia condition lead to enhanced expression of BNIP3 inducing cardiomyocyte death...
October 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29030732/deguelin-induces-puma-mediated-apoptosis-and-promotes-sensitivity-of-lung-cancer-cells-lccs-to-doxorubicin-dox
#19
Aimei Wang, Weina Wang, Yaqi Chen, Fengqiao Ma, Xiaoming Wei, Yongyi Bi
As a natural agent for chemotherapy, deguelin remarkably suppresses proliferation in numerous solid cancers. Nevertheless, the molecular mechanisms of its suppression are still insufficient. In our research, it was revealed that deguelin induced cell death of lung cancer cells (LCCs) by triggering expression of PUMA. Deguelin triggered PUMA induction independently of p53 via suppression of PI3K/AKT pathway, therefore stimulating Foxo3a to bind with PUMA promoter and stimulate its transcription. Subsequent to activation, PUMA motivated Bax as well as the intrinsic mitochondrial cell death pathway...
October 13, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29030599/genome-wide-meta-analysis-associates-hla-dqa1-drb1-and-lpa-and-lifestyle-factors-with-human-longevity
#20
Peter K Joshi, Nicola Pirastu, Katherine A Kentistou, Krista Fischer, Edith Hofer, Katharina E Schraut, David W Clark, Teresa Nutile, Catriona L K Barnes, Paul R H J Timmers, Xia Shen, Ilaria Gandin, Aaron F McDaid, Thomas Folkmann Hansen, Scott D Gordon, Franco Giulianini, Thibaud S Boutin, Abdel Abdellaoui, Wei Zhao, Carolina Medina-Gomez, Traci M Bartz, Stella Trompet, Leslie A Lange, Laura Raffield, Ashley van der Spek, Tessel E Galesloot, Petroula Proitsi, Lisa R Yanek, Lawrence F Bielak, Antony Payton, Federico Murgia, Maria Pina Concas, Ginevra Biino, Salman M Tajuddin, Ilkka Seppälä, Najaf Amin, Eric Boerwinkle, Anders D Børglum, Archie Campbell, Ellen W Demerath, Ilja Demuth, Jessica D Faul, Ian Ford, Alessandro Gialluisi, Martin Gögele, MariaElisa Graff, Aroon Hingorani, Jouke-Jan Hottenga, David M Hougaard, Mikko A Hurme, M Arfan Ikram, Marja Jylhä, Diana Kuh, Lannie Ligthart, Christina M Lill, Ulman Lindenberger, Thomas Lumley, Reedik Mägi, Pedro Marques-Vidal, Sarah E Medland, Lili Milani, Reka Nagy, William E R Ollier, Patricia A Peyser, Peter P Pramstaller, Paul M Ridker, Fernando Rivadeneira, Daniela Ruggiero, Yasaman Saba, Reinhold Schmidt, Helena Schmidt, P Eline Slagboom, Blair H Smith, Jennifer A Smith, Nona Sotoodehnia, Elisabeth Steinhagen-Thiessen, Frank J A van Rooij, André L Verbeek, Sita H Vermeulen, Peter Vollenweider, Yunpeng Wang, Thomas Werge, John B Whitfield, Alan B Zonderman, Terho Lehtimäki, Michele K Evans, Mario Pirastu, Christian Fuchsberger, Lars Bertram, Neil Pendleton, Sharon L R Kardia, Marina Ciullo, Diane M Becker, Andrew Wong, Bruce M Psaty, Cornelia M van Duijn, James G Wilson, J Wouter Jukema, Lambertus Kiemeney, André G Uitterlinden, Nora Franceschini, Kari E North, David R Weir, Andres Metspalu, Dorret I Boomsma, Caroline Hayward, Daniel Chasman, Nicholas G Martin, Naveed Sattar, Harry Campbell, Tōnu Esko, Zoltán Kutalik, James F Wilson
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated...
October 13, 2017: Nature Communications
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