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https://www.readbyqxmd.com/read/29780826/silibinin-induced-human-glioblastoma-cell-apoptosis-concomitant-with-autophagy-through-simultaneous-inhibition-of-mtor-and-yap
#1
Zhuan-Li Bai, Vincent Tay, Shu-Zhong Guo, Juan Ren, Mao-Guo Shu
Silibinin, also known as silybin, is the major flavonolignan isolated from Silybum marianum . Although previous reports demonstrated that silibinin exhibits significant tumor suppressor activities in various cancers by promoting cell apoptosis, it was also shown to trigger autophagy to counteract apoptosis induced by exogenous stresses in several types of cells. However, there is no report to address the role of silibinin induced autophagy in human A172 and SR glioblastoma cells. Our study showed that silibinin treatment not only inhibited the metabolic activities of glioblastoma cells but also promoted their apoptosis through the regulation of caspase 3 and PARP-1 in concentration- and time-dependent manners...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29780409/beneficial-effects-of-resveratrol-mediated-inhibition-of-the-mtor-pathway-in-spinal-cord-injury
#2
REVIEW
Jingying Zhou, Xue Huo, Benson O A Botchway, Luyao Xu, Xiaofang Meng, Songou Zhang, Xuehong Liu
Spinal cord injury (SCI) causes a high rate of morbidity and disability. The clinical features of SCI are divided into acute, subacute, and chronic phases according to its pathophysiological events. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cell death and inflammation in the acute phase and neuroregeneration in the subacute/chronic phases at different times. Resveratrol has the potential of regulating cell growth, proliferation, metabolism, and angiogenesis through the mTOR signaling pathway...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29778718/nimbolide-epigenetically-regulates-autophagy-and-apoptosis-in-breast-cancer
#3
Venkatesh Pooladanda, Soumya Bandi, Sandhya Rani Mondi, Krishna Mohan Gottumukkala, Chandraiah Godugu
Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29777434/ascorbic-acid-inhibits-senescence-in-mesenchymal-stem-cells-through-ros-and-akt-mtor-signaling
#4
Mengkai Yang, Songsong Teng, Chunhui Ma, Yinxian Yu, Peilin Wang, Chengqing Yi
Mesenchymal stem cell (MSC) aging seriously affects its function in stem cell transplantation for treatment. Extensive studies have focused on how to inhibit senescence in MSCs. However, the mechanism of senescence in MSC was not clear. In this study, we used D-galactose to induce MSC aging. Then we found that the number of aging cells was increased compared with untreated MSCs. We discovered that ascorbic acid could inhibit the production of reactive oxygen species (ROS) and activation of AKT/mTOR signaling in MSCs caused by D-galactose...
May 18, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29777330/down-regulating-il-6-gp130-targets-improved-the-anti-tumor-effects-of-5-fluorouracil-in-colon-cancer
#5
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/29777213/semaphorin-6d-reverse-signaling-controls-macrophage-lipid-metabolism-and-anti-inflammatory-polarization
#6
Sujin Kang, Yoshimitsu Nakanishi, Yoshiyuki Kioi, Daisuke Okuzaki, Tetsuya Kimura, Hyota Takamatsu, Shohei Koyama, Satoshi Nojima, Masayuki Nishide, Yoshitomo Hayama, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Tomomi Shimogori, Junichi Takagi, Toshihiko Toyofuku, Atsushi Kumanogoh
Polarization of macrophages into pro-inflammatory or anti-inflammatory states has distinct metabolic requirements, with mechanistic target of rapamycin (mTOR) kinase signaling playing a critical role. However, it remains unclear how mTOR regulates metabolic status to promote polarization of these cells. Here we show that an mTOR-Semaphorin 6D (Sema6D)-Peroxisome proliferator receptor γ (PPARγ) axis plays critical roles in macrophage polarization. Inhibition of mTOR or loss of Sema6D blocked anti-inflammatory macrophage polarization, concomitant with severe impairments in PPARγ expression, uptake of fatty acids, and lipid metabolic reprogramming...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29777202/aberrant-modulation-of-ribosomal-protein-s6-phosphorylation-confers-acquired-resistance-to-mapk-pathway-inhibitors-in-braf-mutant-melanoma
#7
Ming-Zhao Gao, Hong-Bin Wang, Xiang-Ling Chen, Wen-Ting Cao, Li Fu, Yun Li, Hai-Tian Quan, Cheng-Ying Xie, Li-Guang Lou
BRAF and MEK inhibitors have shown remarkable clinical efficacy in BRAF-mutant melanoma; however, most patients develop resistance, which limits the clinical benefit of these agents. In this study, we found that the human melanoma cell clones, A375-DR and A375-TR, with acquired resistance to BRAF inhibitor dabrafenib and MEK inhibitor trametinib, were cross resistant to other MAPK pathway inhibitors. In these resistant cells, phosphorylation of ribosomal protein S6 (rpS6) but not phosphorylation of ERK or p90 ribosomal S6 kinase (RSK) were unable to be inhibited by MAPK pathway inhibitors...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29777201/novel-smoothened-inhibitors-for-therapeutic-targeting-of-na%C3%A3-ve-and-drug-resistant-hedgehog-pathway-driven-cancers
#8
Qing-Rou Li, Hui Zhao, Xue-Sai Zhang, Henk Lang, Ker Yu
The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29776912/targeting-glutaminase-may-overcome-resistance-to-mtor-inhibition
#9
(no author information available yet)
mTOR inhibitor-mediated suppression of glycolysis results in a compensatory increase in glutaminolysis.
May 18, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29775899/hispidulin-alleviates-high-glucose-induced-podocyte-injury-by-regulating-protective-autophagy
#10
Fengbo Wu, Sijia Li, Nan Zhang, Wei Huang, Xiang Li, Manyi Wang, Ding Bai, Bo Han
OBJECTIVES: Diabetic nephropathy (DN) is one of the most common complications in patients with diabetes, and the discovery of novel targeted therapeutic approaches for DN treatment still faces severe challenges. In the current study, we aimed to discover a novel natural product for potential DN treatment and determine its molecular mechanisms. MATERIALS AND METHODS: Methylthiazoltetrazolium (MTT) assay was employed to evaluate cell viability. Transmission electron microscopy, GFP-LC3 fluorescence fusion plasmid, and Annexin V/PI apoptosis assay were carried out to determine cellular autophagy and apoptosis...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775658/hydroxysafflor-yellow-a-protects-brain-microvascular-endothelial-cells-against-oxygen-glucose-deprivation-reoxygenation-injury-involvement-of-inhibiting-autophagy-via-class-i-pi3k-akt-mtor-signaling-pathway
#11
Guang Yang, Ning Wang, Sai Wang Seto, Dennis Chang, Huazheng Liang
The present study aimed to test whether Hydroxysafflor yellow A (HSYA) protects the brain microvascular endothelial cells (BMECs) injury induced by oxygen glucose deprivation/reoxygenation (OGD/R) via the PI3K/Akt/mTOR autophagy signaling pathway. Primary rat BMECs were cultured and identified by the expression of factor VIII-related antigen before being exposed to OGD/R to imitate ischemia/reperfusion (I/R) damage in vitro. The protective effect of HSYA was evaluated by assessing (1) cellular morphologic and ultrastructural changes; (2) cell viability and cytotoxicity; (3) transendothelial electrical resistance (TEER) of monolayer BMECs; (4) cell apoptosis; (5) fluorescence intensity of LC3B; (6) LC3 mRNA expression; (7) protein expressions of LC3, Beclin-1, Zonula occludens-1 (ZO-1), phospho-Akt (p-Akt), Akt, phospho-mTOR (p-mTOR) and mTOR...
May 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29774105/pre-clinical-activity-of-targeting-the-pi3k-akt-mtor-pathway-in-burkitt-lymphoma
#12
Maria Bhatti, Thomas Ippolito, Cory Mavis, Juan Gu, Mitchell S Cairo, Megan S Lim, Francisco Hernandez-Ilizaliturri, Matthew J Barth
Though outcomes for pediatric Burkitt lymphoma (BL) have improved significantly in recent decades with intensive multi-agent chemotherapy and the addition of rituximab, chemotherapy resistance remains a significant impediment to cure following relapse. Activation of the PI3K/AKT pathway has been implicated in Burkitt lymphomagenesis and increased PI3K/AKT activation has been associated with worse outcomes in adults with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Inhibitors of the PI3K/AKT pathway have been approved for the treatment of refractory indolent B-NHL and continue to be investigated for treatment of aggressive B-NHLs...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773990/atorvastatin-inhibits-inflammatory-response-attenuates-lipid-deposition-and-improves-the-stability-of-vulnerable-atherosclerotic-plaques-by-modulating-autophagy
#13
Shi Peng, Long-Wei Xu, Xin-Yu Che, Qing-Qing Xiao, Jun Pu, Qin Shao, Ben He
Atherosclerosis is a chronic disease comprising intima malfunction and arterial inflammation. Recent studies have demonstrated that autophagy could inhibit inflammatory response in atherosclerosis and exert subsequent atheroprotective effects. Our previous study also demonstrated the role of autophagy in the inhibition of inflammation by atorvastatin in vitro . Therefore, in the present study, we aimed to determine whether atorvastatin could upregulate autophagy to inhibit inflammatory cytokines secretion, lipid accumulation, and improve vulnerable plaque stability, both in vitro and in vivo ...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29773580/resistin-inhibits-neuronal-autophagy-through-toll-like-receptor-4
#14
Jie Miao, Yacir Benomar, Sarah Al-Rifai, Ghislaine Poizat, Laure Riffault, Delphine Crepin, Mohammed Taouis
Autophagy is as a non-selective degradation pathway induced in energy-deprived cells and in non-starved cells by participating in cellular inflammatory responses mainly through the elimination of injured and aged mitochondria that constitute an important source of reactive oxygen species. We have previously reported that resistin/TLR4 signaling pathway induces inflammation and insulin resistance in neuronal cell. However, the impact of resistin-induced inflammation on neuronal autophagy is unknown. In the present study, we hypothesized that resistin-induced neuroinflammation could be attributed, at least partially, to the impairment of autophagy pathways in neuronal cells...
May 17, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29773381/cd44-targeted-hyaluronic-acid-curcumin-prodrug-protects-renal-tubular-epithelial-cell-survival-from-oxidative-stress-damage
#15
Jing-Bo Hu, Shu-Juan Li, Xu-Qi Kang, Jing Qi, Jia-Hui Wu, Xiao-Juan Wang, Xiao-Ling Xu, Xiao-Ying Ying, Sai-Ping Jiang, Jian You, Yong-Zhong Du
Based on the abnormally increased expression of CD44 receptors on renal tubule epithelial cells during ischemia/reperfusion-induced acute kidney injury (AKI), we developed a hyaluronic acid-curcumin (HA-CUR) polymeric prodrug targeting to epithelial cells and then relieving oxidative stress damages. The water solubility of HA-CUR was significantly enhanced and approximately 27-fold higher than that of CUR. Cellular uptake test showed HA-CUR was preferably internalized by H2 O2 -pretreated tubular epithelial (HK-2) cells compared with free CUR benefiting from the specific binding between HA and CD44 receptors...
August 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29773107/-over-expression-of-mir-151a-3p-inhibits-proliferation-and-migration-of-pc-3-prostate-cancer-cells
#16
Yi Zhang, Tongtong Hao, Han Zhang, Pengtao Wei, Xiaohui Li
Objective To observe the effect of microRNA-151a-3p (miR-151a-3p) up-regulation on the proliferation and migration of prostate cancer cells and explore the possible molecular mechanism. Methods The expression of miR-151a-3p in PC-3M, C4-2B, 22RV1, DU-145, PC-3, LNCap human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time fluorescence quantitative PCR. PC-3 cells with the lowest expression of miR-151a-3p were used for subsequent experiments. Bioinformatics and dual-luciferase reporter assay were performed to predict and test potential target genes of miR-151a-3p...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29772587/anti-inflammatory-effects-of-cardamonin-in-ovarian-cancer-cells-are-mediated-via-mtor-suppression
#17
Huajiao Chen, Daohua Shi, Peiguang Niu, Yanting Zhu, Jintuo Zhou
Cardamonin exhibits a variety of pharmacological activities including anti-inflammatory and antitumor, which are correlated with the inhibition of nuclear factor-kappaB and the mammalian target of rapamycin, respectively. However, whether the anti-inflammatory effects of cardamonin are mediated by the mammalian target of rapamycin remains unknown. In this study, ovarian cancer SKOV3 cells were cultured with lipopolysaccharide to induce inflammation, and the inhibitory effects and underlying molecular mechanisms of cardamonin were investigated using specific inhibitors of the mammalian target of rapamycin and the nuclear factor-kappaB pathway (rapamycin and pyrrolidine dithiocarbamate, respectively)...
May 17, 2018: Planta Medica
https://www.readbyqxmd.com/read/29768192/nuclear-export-inhibition-enhances-hlh-30-tfeb-activity-autophagy-and-lifespan
#18
Melissa J Silvestrini, Joseph R Johnson, Anita V Kumar, Tara G Thakurta, Karine Blais, Zachary A Neill, Sarah W Marion, Victoria St Amand, Robert A Reenan, Louis R Lapierre
Transcriptional modulation of the process of autophagy involves the transcription factor HLH-30/TFEB. In order to systematically determine the regulatory network of HLH-30/TFEB, we performed a genome-wide RNAi screen in C. elegans and found that silencing the nuclear export protein XPO-1/XPO1 enhances autophagy by significantly enriching HLH-30 in the nucleus, which is accompanied by proteostatic benefits and improved longevity. Lifespan extension via xpo-1 silencing requires HLH-30 and autophagy, overlapping mechanistically with several established longevity models...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767256/umbilical-cord%C3%A2-derived-mesenchymal-stem-cells-can-inhibit-the-biological-functions-of-melanoma-a375-cells
#19
Wei Wang, Li Li, Fei Chen, Yu Yang
Tumor tropism is an important property of mesenchymal stem cells (MSCs) that has been used in tumor‑targeting therapies. However, the effects of MSCs on tumors remain controversial. The aim of the present study was to investigate the effects of MSCs on A375 melanoma cells. Umbilical cord‑derived mesenchymal stem cells (UCMSCs) were co‑cultured with A375 cells. MTT and Transwell assays were used to assess cell proliferation and invasion, while flow cytometry was performed to detect the apoptosis and the cell cycle distribution of A375 cells...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29765528/metabolic-changes-associated-with-metformin-potentiates-bcl-2-inhibitor-venetoclax-and-cdk9-inhibitor-bay1143572-and-reduces-viability-of-lymphoma-cells
#20
Vineela Chukkapalli, Leo I Gordon, Parameswaran Venugopal, Jeffrey A Borgia, Reem Karmali
Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines...
April 20, 2018: Oncotarget
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