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https://www.readbyqxmd.com/read/29777330/down-regulating-il-6-gp130-targets-improved-the-anti-tumor-effects-of-5-fluorouracil-in-colon-cancer
#1
Sanhong Li, Jilai Tian, Hongming Zhang, Shoubing Zhou, Xiyong Wang, Lei Zhang, Jiapeng Yang, Zhigang Zhang, Zhenling Ji
Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor. Thus, we speculated that in colon cancer, the anti-tumor efficacy of 5-FU might be increased in combination with IL-6/GP130 inhibitors...
May 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29775573/indole-3-carbinol-i3c-enhances-the-sensitivity-of-murine-breast-adenocarcinoma-cells-to-doxorubicin-dox-through-inhibition-of-nf-%C3%AE%C2%BA%C3%AE-blocking-angiogenesis-and-regulation-of-mitochondrial-apoptotic-pathway
#2
Subhadip Hajra, Arup Ranjan Patra, Abhishek Basu, Prosenjit Saha, Sudin Bhattacharya
Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of naturally occurring glucosinolate breakdown product Indole-3-Carbinol (I3C) as well as its abilities to induce selective cell death towards malignant cell. Therefore, the objective of the present study is to improve the therapeutic efficacy and prevention of doxorubicin (DOX)-induced toxicity, by the concurrent use of Indole-3-Carbinol (I3C). In this study, I3C was administered (20 mg/kg b.w., p...
May 15, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29774773/mir-711-induced-down-regulation-of-angiopoietin-1-mediates-neuronal-cell-death
#3
Boris Sabirzhanov, Alan Faden, Taryn Aubrecht, Rebecca Henry, Ethan Glaser, Bogdan A Stoica
Angiopoietin-1 (Ang-1) is a well-known endothelial growth factor but its effects on neurons have yet to be elucidated. We show that Ang-1 is rapidly down-regulated in the injured brain after controlled cortical impact (CCI), a mouse experimental TBI model and in etoposide-induced neuronal apoptosis in vitro. Ang-1 treatment inhibits etoposide-induced up-regulation of pro-apoptotic Bcl-2 family members Noxa, Puma, Bim, and Bax; reduces markers of caspase-dependent (cytochrome c release/caspase activation) and caspase-independent (apoptosis-inducing factor release) pathways; and limits neuronal cell death...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29769286/targeted-inhibition-of-histone-h3k27-demethylation-is-effective-in-high-risk-neuroblastoma
#4
Timothy L Lochmann, Krista M Powell, Jungoh Ham, Konstantinos V Floros, Daniel A R Heisey, Richard I J Kurupi, Marissa L Calbert, Maninderjit S Ghotra, Patricia Greninger, Mikhail Dozmorov, Madhu Gowda, Andrew J Souers, C Patrick Reynolds, Cyril H Benes, Anthony C Faber
High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death...
May 16, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29767411/mek1-2-inhibition-by-binimetinib-is-effective-as-a-single-agent-and-potentiates-the-actions-of-venetoclax-and-abt-737-under-conditions-that-mimic-the-chronic-lymphocytic-leukaemia-cll-tumour-microenvironment
#5
Kyle Crassini, Yandong Shen, William S Stevenson, Richard Christopherson, Chris Ward, Stephen P Mulligan, O Giles Best
The survival and proliferation of chronic lymphocytic leukaemia (CLL) cells is driven by multiple signalling pathways, including those mediated by the B cell, Toll-like and chemokine receptors. Many of these pathways converge on the same signalling molecules, including those involved in the Raf-1/MEK/Erk1/2-MAPK pathway. We investigated the effects of the MEK1/2 (also termed MAP2K1/2) inhibitor, binimetinib, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment. Binimetinib blocked CLL cell survival induced by stroma-conditioned media and phorbol myristylate (PMA)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29755657/regulatory-effect-of-anti-gp130-functional-mab-on-il-6-mediated-rankl-and-wnt5a-expression-through-jak-stat3-signaling-pathway-in-fls
#6
Ping Miao, Xiao Wei Zhou, Ping Wang, Rong Zhao, Ninan Chen, Chao Ying Hu, Xue Hua Chen, Liu Qian, Qi Wen Yu, Ji Ying Zhang, Rong Xu, Dong Yi He, Lian Bo Xiao, Pu Li, Mason Lu, Dong Qing Zhang
We investigated the effect on rheumatoid arthritis (RA) of an anti-gp130 monoclonal antibody (mAb) and its mechanism using RA fibroblast-like synoviocytes (FLS) and a collagen antibody-induced arthritis (CAIA) mouse model. We determined the interleukin 6 (IL-6), IL-6 receptor α (IL-6Rα), gp130, receptor activator of nuclear factor κB ligand (RANKL), matrix metalloproteinase 3 (MMP3), TIMP metallopeptidase inhibitor 1 (TIMP1), and Bcl-2 levels in RA and osteoarthritis (OA) serum and synovial fluid. RA FLS were cultured with or without IL-6/IL-6Rα; WNT5A and RANKL levels were detected...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752433/palmitic-acid-but-not-high-glucose-induced-myocardial-apoptosis-is-alleviated-by-n%C3%A2-acetylcysteine-due-to-attenuated-mitochondrial-derived-ros-accumulation-induced-endoplasmic-reticulum-stress
#7
Yang He, Lingyun Zhou, Zhiqiang Fan, Shikun Liu, Weijin Fang
Pharmacological inhibition of reactive oxygen species (ROS) is a potential strategy to prevent diabetes-induced cardiac dysfunction. This study was designed to investigate precise effects of antioxidant N‑acetylcysteine (NAC) in alleviating diabetic cardiomyopathy (DCM). Echocardiography and histologic studies were performed 12 weeks after streptozocin injection. Protein levels involved in endoplasmic reticulum stress (ERS) and apoptosis were analyzed by western blotting in diabetic hearts or high-glucose (HG, 30 mM)- and palmitic acid (PA, 300 μM)-cultured neonatal rat cardiomyocytes (NRCMs)...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29750888/adiponectin-enhances-biological-functions-of-vascular-endothelial-progenitor-cells-through-the-mtor-stat3-signaling-pathway
#8
Xiaoying Dong, Xia Yan, Wei Zhang, Shengqiu Tang
Adiponectin (APN), an adipose tissue-excreted adipokine, plays protective roles in metabolic and cardiovascular diseases. In this study, the effects and mechanisms of APN on biological functions of rat vascular endothelial progenitor cells (VEPCs) were investigated in vitro. After administrating APN in rat VEPCs, the proliferation was measured by methyl thiazolyl tetrazolium (MTT) method, the apoptotic rate was test by Flow cytometry assay, mRNA expression of B-cell lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) was determined by Real-time reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression of mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (pSTAT3) was analyzed by Western Blot...
May 10, 2018: Physiological Research
https://www.readbyqxmd.com/read/29744879/blocking-nox2-improves-mesenchymal-stem-cells-therapy-in-myocardial-infarction-via-antagonizing-oxidant-and-promoting-survival
#9
Dan Feng, Lai Zhang, Fengzhi Ding, Fan Yang, Wenya Ma, Zhenbo Han, Bingjie Hua, Xiuxiu Wang, Ying Yu, Qi Huang, Lei Lei, Zhenwei Pan, Benzhi Cai
An increase in reactive oxygen species (ROS) plays a key role in aging and apoptosis in mesenchymal stem cells derived from bone marrow (BMSCs). NADPH oxidase Nox2 serves as an important source of intracellular ROS formation. This study is designed to determine if blocking Nox2 enhances anti-apoptotic and anti-aging ability of BMSCs to oxidant stress, and thus improves therapeutic efficacy in myocardial infarction (MI). Nox2 inhibitor (Acetovanillone) and Nox2 siRNA were used to block Nox2 in BMSCs, and the cell viability, apoptosis, senescence and survival of BMSCs were determined by CCK-8, Edu staining, TUNEL staining, β-galactosidase (β-gal) assay and DAPI labeling...
May 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29743821/blockade-of-itga2-induces-apoptosis-and-inhibits-cell-migration-in-gastric-cancer
#10
Yu-Chang Chuang, Hsin-Yi Wu, Yu-Ling Lin, Shey-Cherng Tzou, Cheng-Hsun Chuang, Ting-Yan Jian, Pin-Rong Chen, Yuan-Ching Chang, Chi-Hsin Lin, Tse-Hung Huang, Chao-Ching Wang, Yi-Lin Chan, Kuang-Wen Liao
Background: Gastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration...
2018: Biological Procedures Online
https://www.readbyqxmd.com/read/29737939/qianlongtong-inhibits-proliferation-and-induces-apoptosis-of-hyperplastic-prostate-cells
#11
Yifeng Yuan, Jing Yang, Wenxiong Zhu, Tao Liu, JuQiao He, Qing Zhou, Xing Zhou, Xi Zhang
Qianlongtong is a compound made from traditional Chinese herbs and it has proven to be very effective to treat patients with benign prostate hypertrophy. However, its mechanism is still unknown. This study is designed to investigate the effect of Qianlongtong on proliferation and apoptosis of hyperplastic prostate cells. Flow cytometry (FCM) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were used to assess proliferation and apoptosis of hyperplastic prostate cells in the following groups: control group, tamoxifen group, and groups with low, moderate, and high dosage of Qianlongtong...
May 1, 2018: American Journal of Men's Health
https://www.readbyqxmd.com/read/29733883/distinct-apoptotic-blocks-mediate-resistance-to-panher-inhibitors-in-her2-breast-cancer-cells
#12
Bahriye Karakas, Yeliz Ozmay, Huveyda Basaga, Ozgur Gul, Ozgur Kutuk
Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells...
May 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29731711/artemisinin-prevents-glutamate-induced-neuronal-cell-death-via-akt-pathway-activation
#13
Shao-Peng Lin, Wenjun Li, Ali Winters, Ran Liu, Shao-Hua Yang
Artemisinin is an anti-malarial drug that has been in use for almost half century. Recently, novel biological effects of artemisinin on cancer, inflammation-related disorders and cardiovascular disease were reported. However, neuroprotective actions of artemisinin against glutamate-induced oxidative stress have not been investigated. In the current study, we determined the effect of artemisinin against oxidative insult in HT-22 mouse hippocampal cell line. We found that pretreatment of artemisinin declined reactive oxygen species (ROS) production, attenuated the collapse of mitochondrial membrane potential induced by glutamate and rescued HT-22 cells from glutamate-induced cell death...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29730189/design-synthesis-and-biological-evaluation-of-benzo-cd-indol-2-1h-ones-derivatives-as-brd4-inhibitors
#14
Yuxin Feng, Senhao Xiao, Yantao Chen, Hao Jiang, Na Liu, Cheng Luo, Shijie Chen, Hua Chen
Compound 1 bearing with benzo [cd]indol-2(1H)-one scaffold was identified as an effective BRD4 inhibitor through the AlphaScreen-based high-throughput screening and its high-resolution crystal structure with BRD4_BD1 protein. A series of 48 compounds were designed and synthesized by structural optimization on compound 1. All the compounds have been evaluated for their BRD4 inhibitory activities. The results showed that compounds 23, 24, 28 and 44 are the most potential ones with the IC50 values of 1.02 μM, 1...
April 28, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29729261/zoledronic-acid-induces-micronuclei-formation-mitochondrial-mediated-apoptosis-and-cytostasis-in-kidney-cells
#15
Soma Shiva Nageswara Rao Singireesu, Sujan Kumar Mondal, Suresh Yerramsetty, Sunil Misra
AIMS: Zoledronic acid (ZA), a FDA approved drug has used widely in the treatment of bone metastasis complications, has been linked to renal toxicity with unclear mechanism. The present study is aimed at investigating genotoxic and cytotoxic effects of ZA in renal epithelial cells. MAIN METHODS: The genotoxic effect of ZA in Vero and MDCK cells determined by cytokinesis block micronucleus (CBMN) assay. The cytotoxic effect assessed by analysing cell cycle profile, cell death and mitochondrial membrane potential by flow cytometry using propidium iodide, AnnexinV-FITC/PI and JC1 dye staining, respectively, BAX and Bcl-2 expression by Western blotting and caspase activity by spectrofluorimetry...
May 2, 2018: Life Sciences
https://www.readbyqxmd.com/read/29727714/inhibitory-effect-of-microrna-154-targeting-whsc1-on-cell-proliferation-of-human-skin-squamous-cell-carcinoma-through-mediating-the-p53-signaling-pathway
#16
Hong-Quan Chen, Dong Gao
OBJECTIVE: Skin squamous cell carcinoma (SCC) is a common, morbid, and frequently lethal malignancy and ranks as the sixth most deadly cancer worldwide. Hence, this study aims to explore the effect of microRNA-154 (miR-154) targeting WHSC1 on proliferation and apoptosis of SCC cells via the P53 signaling pathway. METHODS: The targeting relationship between WHSC1 and miR-154 was validated using dual-luciferase reporter assay. Normal human epidermal keratinocytes (NHEK) were included, and SCC A431 and SCC-15 cell lines were cultured and transfected with miR-154 mimic, miR-154 inhibitor or siRNA-WHSC1...
May 1, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29725084/loss-of-tctn3-causes-neuronal-apoptosis-and-neural-tube-defects-in-mice
#17
Bin Wang, Yingying Zhang, Hongli Dong, Siyi Gong, Bin Wei, Man Luo, Hongyan Wang, Xiaohui Wu, Wei Liu, Xingshun Xu, Yufang Zheng, Miao Sun
Tctn3 belongs to the Tectonic (Tctn) family and is a single-pass membrane protein localized at the transition zone of primary cilia as an important component of ciliopathy-related protein complexes. Previous studies showed that mutations in Tctn1 and Tctn2, two members of the tectonic family, have been reported to disrupt neural tube development in humans and mice, but the functions of Tctn3 in brain development remain elusive. In this study, Tctn3 knockout (KO) mice were generated by utilizing the piggyBac (PB) transposon system...
May 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29722068/differential-ability-of-formononetin-to-stimulate-proliferation-of-endothelial-cells-and-breast-cancer-cells-via-a-feedback-loop-involving-microrna-375-rasd1-and-er%C3%AE
#18
Jian Chen, Xing Zhang, Yong Wang, Yu Ye, Zhaoquan Huang
For postmenopausal cardiovascular disease, long-term estrogen therapy may increase the risk of breast cancer. To reduce this risk, estrogen may be replaced with the phytoestrogen formononetin, but how formononetin acts on vascular endothelial cells (ECs) and breast cancer cells is unclear. Here, we show that low concentrations of formononetin induced proliferation and inhibited apoptosis more strongly in cultured human umbilical vein endothelial cells (HUVECs) than in breast cancer cells expressing estrogen receptor α (ERα) (MCF-7, BT474) or not (MDA-MB-231), and that this differential stimulation was associated with miR-375 up-regulation in HUVECs...
May 2, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29717768/breviscapine-ameliorates-ccl4%C3%A2-induced-liver-injury-in-mice-through-inhibiting-inflammatory-apoptotic-response-and-ros-generation
#19
Yu Liu, Pei-Hao Wen, Xin-Xue Zhang, Yang Dai, Qiang He
Acute liver injury is characterized by fibrosis, inflammation and apoptosis, leading to liver failure, cirrhosis or cancer and affecting the clinical outcome in the long term. However, no effective therapeutic strategy is currently available. Breviscapine, a mixture of flavonoid glycosides, has been reported to have multiple biological functions. The present study aimed to investigate the effects of breviscapine on acute liver injury induced by CCl4 in mice. C57BL/6 mice were subjected to intraperitoneal injection with CCl4 for 8 weeks with or without breviscapine (15 or 30 mg/kg)...
May 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29709909/induction-of-apoptosis-by-citrus-unshiu-peel-in-human-breast-cancer-mcf-7-cells-involvement-of-ros-dependent-activation-of-ampk
#20
Min Yeong Kim, Hyun Hwang Bo, Eun Ok Choi, Da He Kwon, Hong Jae Kim, Kyu Im Ahn, Seon Yeong Ji, Jin-Woo Jeong, Shin-Hyung Park, Su-Hyun Hong, Gi-Young Kim, Cheol Park, Heui-Soo Kim, Sung-Kwon Moon, Seok-Joong Yun, Wun Jae Kim, Yung Hyun Choi
The fruit of Citrus unshiu MARKOVICH used for various purposes in traditional medicine has various pharmacological properties including antioxidant, anti-inflammatory, and antibacterial effects. Recently, the possibility of anti-cancer activity of the extracts or components of this fruit has been reported; however, the exact mechanism has not yet been fully understood. In this study, we evaluated the anti-proliferative effect of water extract of C. unshiu peel (WECU) on human breast cancer MCF-7 cells and investigated the underlying mechanism...
2018: Biological & Pharmaceutical Bulletin
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