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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/28436000/foxo3a-suppression-and-vps34-activity-are-essential-to-anti-atrophic-effects-of-leucine-in-skeletal-muscle
#1
Igor L Baptista, João G Silvestre, William J Silva, Siegfried Labeit, Anselmo S Moriscot
Our aim is to gain insight into the mechanisms underlying the anti-atrophic effects of leucine, namely, the way that this amino acid can restrain the up-regulation of MuRF1 and Mafbx/Atrogin-1 in muscle atrophy. Male rats received dietary leucine supplementation for 1-3 days, during which time their hind limbs were immobilized. Our results showed that leucine inhibited Forkhead Box O3 (FoxO3a) translocation to cell nuclei. In addition, leucine was able to reverse the expected reduction of FoXO3a ubiquitination caused by immobilization...
April 24, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28435223/efficacy-of-the-dual-pi3k-and-mtor-inhibitor-nvp-bez235-in-combination-with-imatinib-mesylate-against-chronic-myelogenous-leukemia-cell-lines
#2
Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu
BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine kinase inhibitor in vitro. METHODS: Two human CML cell lines, K562 and KBM7R (T315I mutant strain), were used. The proliferation of CML cells was detected by MTS (Owen's reagent) assay...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28433890/il-37-induces-autophagy-in-hepatocellular-carcinoma-cells-by-inhibiting-the-pi3k-akt-mtor-pathway
#3
Ting-Ting Li, Di Zhu, Tong Mou, Zhen Guo, Jun-Liang Pu, Qing-Song Chen, Xu-Fu Wei, Zhong-Jun Wu
Autophagy is an intracellular "self-eating" process that is closely related to inflammation and cellular immunity. New studies indicate that autophagy is also involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL-37) has been shown to have tumor-suppressive abilities in hepatocellular carcinoma (HCC). Notably, autophagy appears to play a dual role in the development of HCC and may be involved in both tumorigenesis and tumor suppression. However, the potential role of IL-37 in autophagy is currently unknown...
April 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28428363/phlpp-a-putative-cellular-target-during-insulin-resistance-and-type-2-diabetes
#4
Alpana Mathur, Vivek Kumar Pandey, Poonam Kakkar
Progressive research in the past decade converges to the impact of PHLPP (Pleckstrin homology domain and leucine rich repeat protein phosphatase) in regulating the cellular metabolism through PI3K/Akt inhibition. Defects in the PKB/Akt signaling coordinates with impaired insulin secretion and insulin resistance, identified during T2D, obesity and cardiovascular disorders which brings in the relevance of PHLPPs in the metabolic paradigm. In this review, we discuss the impact of PHLPP isoforms in insulin signaling and its associated cellular events including mitochondrial dysfunction, DNA damage, autophagy and cell death...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28427045/mir-142-3p-overexpression-increases-chemo-sensitivity-of-nsclc-by-inhibiting-hmgb1-mediated-autophagy
#5
Yuqing Chen, Xin Zhou, Jianou Qiao, Aihua Bao
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high mortality rate. Drug resistance represents a main obstacle in NSCLC treatment. High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells by activating protective autophagy. METHODS: In the current study, we investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1-mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in vitro and in vivo...
March 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28408883/alisol-a-24-acetate-and-alisol-b-23-acetate-induced-autophagy-mediates-apoptosis-and-nephrotoxicity-in-human-renal-proximal-tubular-cells
#6
Chunfei Wang, Liang Feng, Liang Ma, Haifeng Chen, Xiaobin Tan, Xuefeng Hou, Jie Song, Li Cui, Dan Liu, Juan Chen, Nan Yang, Jing Wang, Ying Liu, Bingjie Zhao, Gang Wang, Yuanli Zhou, Xiaobin Jia
Two natural compounds alisol A 24-acetate (24A) and alisol B 23-acetate (23B) are abundant in Rhizoma alismatis. In the present study, we evaluated the induction of 24A and 23B on apoptosis and possible nephrotoxicity of human renal proximal tubular (HK-2) cells by activating autophagy and also explored its regulation on PI3K/Akt/mTOR signaling pathway. Presently, Clusterin, Kim-1, and TFF-3 were considered to be new bioindicators of nephrotoxicity. Interestingly, the protein expression and mRNA levels of Clusterin, Kim-1 and TFF-3 could be significantly increased by 23B and 24A in vivo and in vitro...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28408137/4-acetylantroquinonol-b-suppresses-autophagic-flux-and-improves-cisplatin-sensitivity-in-highly-aggressive-epithelial-cancer-through-the-pi3k-akt-mtor-p70s6k-signaling-pathway
#7
Mingche Liu, Oluwaseun Adebayo Bamodu, Wen-Chien Huang, Muhammad Ary Zucha, Yen-Kuang Lin, Alexander T H Wu, Chun-Chih Huang, Wei-Hwa Lee, Chiou-Chung Yuan, M Hsiao, Li Deng, Yew-Min Tzeng, Chi-Tai Yeh
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg)...
April 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28407045/novel-pathogenesis-regulation-of-apoptosis-by-apelin-apj-system
#8
Jiaqi Liu, Meiqing Liu, Linxi Chen
Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in various diseases through different signal pathways. In this review, we discuss the possible mechanisms by which the Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase (PI3K)/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion (I/R) injury, pulmonary artery hypertension, retinal neovascular disease, acute renal injury, skeletal homeostasis, and gastrointestinal diseases...
April 12, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28402274/magnesium-isoglycyrrhizinate-shows-hepatoprotective-effects-in-a-cyclophosphamide-induced-model-of-hepatic-injury
#9
Wenjiao Jiang, Jingyan Liu, Peijin Li, Qianfeng Lu, Xue Pei, Yilin Sun, Guangji Wang, Kun Hao
The purpose of the current study was to investigate the effect of Magnesium Isoglycyrrhizinate (GM) on cyclophosphamide (CP)-induced hepatic injury in vivo and in vitro. The results demonstrated that GM exerted a protective effect on CP-induced acute liver injury, as evidenced by the alleviations of hepatic pathological damage and serum transaminase activities. Meantime, GM attenuated serum and HepG2 cell supernatant levels of TNF-α, IL-6, IL-1β, SOD and MDA. Western blot results presented that GM down-regulated the expressions of the microtubule associated protein 1A/1B-light chain 3 (LC3), Lysosome associated membrane protein-1 (LAMP-1), p-phosphatidylinositol 3-kinase (PI3K), p-protein Kinase B(Akt), p-mechanistic target of rapamycin(mTOR), p-ribosomal protein S6 kinase 70 kDa (p70S6K), p-4E binding protein 1(4EBP1), p- inhibitor of NF-κB(IκB)α and p-nuclear factor kappa B(NF-κB)p65 in CP-stimulated hepatic tissue and HepG2 cells...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28392425/t-cadherin-promotes-autophagy-and-survival-in-vascular-smooth-muscle-cells-through-mek1-2-erk1-2-axis-activation
#10
Emmanouil Kyriakakis, Agne Frismantiene, Boris Dasen, Dennis Pfaff, Olga Rivero, Klaus-Peter Lesch, Paul Erne, Therese J Resink, Maria Philippova
Autophagy is an evolutionary conserved intracellular catabolic process of vital importance to cell and tissue homeostasis. Autophagy is implicated in the pathogenesis of atherosclerosis but participating cells, molecular mechanisms and functional outcomes have not been fully elucidated. T-cadherin, an atypical glycosylphosphatidylinositol-anchored member of the cadherin superfamily of adhesion molecules, is upregulated on smooth muscle cells (SMCs)(1) in atherosclerotic lesions. Here, using rat and murine aortic SMCs as experimental models, we surveyed the ability of T-cadherin to regulate autophagy in SMCs during serum-starvation stress...
April 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28390196/pi3k-isoform-inhibition-associated-with-anti-bcr-abl-drugs-shows-in-vitro-increased-anti-leukemic-activity-in-philadelphia-chromosome-positive-b-acute-lymphoblastic-leukemia-cell-lines
#11
Simona Ultimo, Carolina Simioni, Alberto M Martelli, Giorgio Zauli, Camilla Evangelisti, Claudio Celeghini, James A McCubrey, Giorgia Marisi, Paola Ulivi, Silvano Capitani, Luca M Neri
B-acute lymphoblastic leukemia (B-ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. Philadelphia chromosome-positive (Ph+) B-ALL is a subtype that expresses the Bcr-Abl fusion protein which represents a negative prognostic factor. Constitutive activation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) network is a common feature of B-ALL, influencing cell growth and survival. In the present study, we aimed to investigate the efficacy of PI3K isoform inhibition in B-ALL cell lines harboring the Bcr-Abl fusion protein...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386360/neuroprotective-effect-of-mir-665-against-sevoflurane-anesthesia-induced-cognitive-dysfunction-in-rats-through-pi3k-akt-signaling-pathway-by-targeting-insulin-like-growth-factor-2
#12
Xihua Lu, Shuaiguo Lv, Yan Mi, Lei Wang, Gensheng Wang
The aim of this study was to investigate the in vivo and in vitro effects of miR-665 on sevoflurane anesthesia-induced cognitive dysfunction. SH-SY5Y cells and male SD rats were treated with sevoflurane to simulate anesthesia-induced cognitive dysfunction. The cells and rats both were transfected with a miR-665 mimic, inhibitor, scramble, IGF-2 siRNA, or treated with P13K/Akt inhibitor LY294002. The cell apoptosis, autophagy, growth related proteins, and mRNA levels were measured using different methods. The motor performance was assessed using the Morris water maze (MWM) test...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386317/alisertib-induces-g2-m-arrest-apoptosis-and-autophagy-via-pi3k-akt-mtor-and-p38-mapk-mediated-pathways-in-human-glioblastoma-cells
#13
Zheng Liu, Feng Wang, Zhi-Wei Zhou, He-Chun Xia, Xin-Yu Wang, Yin-Xue Yang, Zhi-Xu He, Tao Sun, Shu-Feng Zhou
Glioblastoma (GBM) is the most common brain tumor with poor response to current therapeutics. Alisertib (ALS), a second-generation selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects on solid tumors in animal studies. This study aimed to investigate the killing effect of ALS on GBM cell line DAOY and the possible underlying mechanisms using both bioinformatic and cell-based approaches. Our molecular docking showed that ALS preferentially bound AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28374807/sesamol-induces-human-hepatocellular-carcinoma-cells-apoptosis-by-impairing-mitochondrial-function-and-suppressing-autophagy
#14
Zhigang Liu, Bo Ren, Yihui Wang, Chen Zou, Qinglian Qiao, Zhijun Diao, Yashi Mi, Di Zhu, Xuebo Liu
Sesamol, a nutritional phenolic antioxidant compound enriched in sesame seeds, has been shown to have potential anticancer activities. This study aims at characterizing the antitumor efficacy of sesamol and unveiling the importance of mitochondria in sesamol-induced effects using a human hepatocellular carcinoma cell line, HepG2 cells. Results of this study showed that sesamol treatment suppressed colony formation, elicited S phase arrest during cell cycle progression, and induced both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28374157/chalcone-flavokawain-b-induces-autophagic-cell-death-via-reactive-oxygen-species-mediated-signaling-pathways-in-human-gastric-carcinoma-and-suppresses-tumor-growth-in-nude-mice
#15
Chia-Ting Chang, You-Cheng Hseu, Varadharajan Thiyagarajan, Kai-Yuan Lin, Tzong-Der Way, Mallikarjuna Korivi, Jiuun-Wang Liao, Hsin-Ling Yang
Flavokawain B (FKB), a naturally occurring chalcone in kava extracts, has been reported to possess anticancer activity. However, the effect of FKB on gastric cancer remains unclear. We examined the in vitro and in vivo anticancer activity and autophagy involvement of FKB and determined the underlying molecular mechanisms. FKB is potently cytotoxic to human gastric cancer cells (AGS/NCI-N87/KATO-III/TSGH9201) and mildly toxic towards normal (Hs738) cells and primary mouse hepatocytes. FKB-induced AGS cell death was characterized by autophagy, not apoptosis, as evidenced by increased LC3-II accumulation, GFP-LC3 puncta and acidic vesicular organelles (AVOs) formation, without resulting procaspase-3/PARP cleavage...
April 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28359246/in-silico-in-vitro-identification-of-structure-activity-relationship-pattern-of-serpentine-gallic-acid-targeting-pi3k%C3%AE-as-potential-anticancer-target
#16
Pooja Sharma, Aparna Shukla, Komal Kalani, Vijaya Dubey, Suaib Luqman, S K Srivastava, Feroz Khan
Natural products showed anticancer activity and often induce apoptosis or autophagy in cancer cells through the PI3K/Akt/mTOR signaling pathways. The potential of natural products as PI3Ks inhibitors has been reported, which suggest PI3Ks a promising anticancer target. Phosphoinositide 3-kinase (PI3K) is a family of related intracellular signal transducer enzymes or lipid kinases that regulate different cellular processes involved in cancer. In the studied work, anticancer potential of two active plant secondary metabolites, namely gallic acid and serpentine was evaluated against PI3Ks, especially gamma isoform and compared with the wortmannin, a steroid metabolite of the fungi and a non-specific covalent known inhibitor of PI3Ks, based on in-silico QSAR, molecular docking, eADMET and in-vitro activity...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359198/anticancer-properties-and-pharmaceutical-applications-of-plumbagin-a-review
#17
Yuling Liu, Yuee Cai, Chengwei He, Meiwan Chen, Hui Li
It has been shown that plumbagin, a bioactive naphthoquinone isolated from three major plant families viz. Plumbaginaceae, Ebenceae and Droseraceae, definitively exhibits anticancer potential in diverse cancer cells both in vitro and in vivo. Plumbagin shows antineoplastic effects via multi-channel molecular mechanisms, including the induction of apoptosis and autophagy, the disruption of the cell cycle, the inhibition of invasion and metastasis, and anti-angiogenesis. Plumbagin inhibits the growth of cancer cells mainly through the modulation of the signals of PI3K/Akt/mTOR, AMPK, Ras, and so on...
March 30, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28355296/tetraarsenic-hexoxide-induces-g2-m-arrest-apoptosis-and-autophagy-via-pi3k-akt-suppression-and-p38-mapk-activation-in-sw620-human-colon-cancer-cells
#18
Arulkumar Nagappan, Won Sup Lee, Jeong Won Yun, Jing Nan Lu, Seong-Hwan Chang, Jae-Hoon Jeong, Gon Sup Kim, Jin-Myung Jung, Soon Chan Hong
Tetraarsenic hexoxide (As4O6) has been used in Korean folk medicines for the treatment of cancer, however its anti-cancer mechanisms remain obscured. Here, this study investigated the anti-cancer effect of As4O6 on SW620 human colon cancer cells. As4O6 has showed a dose-dependent inhibition of SW620 cells proliferation. As4O6 significantly increased the sub-G1 and G2/M phase population, and Annexin V-positive cells in a dose-dependent manner. G2/M arrest was concomitant with augment of p21 and reduction in cyclin B1, cell division cycle 2 (cdc 2) expressions...
2017: PloS One
https://www.readbyqxmd.com/read/28350056/notoginsenoside-r1-attenuates-glucose-induced-podocyte-injury-via-the-inhibition-of-apoptosis-and-the-activation-of-autophagy-through-the-pi3k-akt-mtor-signaling-pathway
#19
Guodong Huang, Bingyu Zou, Jianzhen Lv, Tongyu Li, Guoli Huai, Shaowei Xiang, Shilong Lu, Huan Luo, Yaping Zhang, Yi Jin, Yi Wang
Injury to terminally differentiated podocytes contributes ignificantly to proteinuria and glomerulosclerosis. The aim of this study was to examine the protective effects of notoginsenoside R1 (NR1) on the maintenance of podocyte number and foot process architecture via the inhibition of apoptosis, the induction of autophagy and the maintenance pf podocyte biology in target cells. The effects of NR1 on conditionally immortalized human podocytes under high glucose conditions were evaluated by determining the percentage apoptosis, the percentage autophagy and the expression levels of slit diaphragm proteins...
January 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28349827/staurosporine-suppresses-survival-of-hepg2-cancer-cells-through-omi-htra2-mediated-inhibition-of-pi3k-akt-signaling-pathway
#20
Youming Ding, Bin Wang, Xiaoyan Chen, Yu Zhou, Jianhui Ge
Staurosporine, which is an inhibitor of a broad spectrum of protein kinases, has shown cytotoxicity on several human cancer cells. However, the underlying mechanism is not well understood. In this study, we examined whether and how this compound has an inhibitory action on phosphatidylinositol 3-kinase (PI3K)/Akt pathway in vitro using HepG2 human hepatocellular carcinoma cell line. Cell viability and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, respectively...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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