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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/29349457/effects-of-tetrahedral-dna-nanostructures-on-autophagy-in-chondrocytes
#1
Sirong Shi, Shiyu Lin, Yong Li, Tao Zhang, Xiaoru Shao, Taoran Tian, Tengfei Zhou, Qianshun Li, Yunfeng Lin
Tetrahedral DNA nanostructures (TDNs) have gathered great attention and are being widely used in biomedicine. We demonstrated that autophagy increased after exposure to TDNs (250 nM) along with the up-regulation of several autophagy-related genes and proteins. TDNs enhanced cell autophagy through the PI3K/AKT/mTOR signaling pathway.
January 19, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29340859/comparative-proteomics-of-chromium-transformed-beas-2b-cells-by-2d-dige-and-maldi-tof-tof-ms
#2
Jian Lu, Miaomiao Tang, Yi Liu, Jin Wang, Zhanao Wu
Chromium (Cr) is a highly toxic, common heavy metal used in industrial production. There are two types of Cr in nature: hexavalent chromium (Cr(VI)) and chromium trichloride (Cr(III)). Cr(III) is involved in the metabolism of sugars and lipids, whereas Cr(VI) is absorbed through the respiratory tract and skin and generates free radicals that result in secondary toxicity. Cr(VI) leads to cancer in the occupational population and is therefore recognized as a human carcinogen by the International Agency for Research on Cancer...
January 16, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29340093/leucine-mediates-autophagosome-lysosome-fusion-and-improves-sperm-motility-by-activating-the-pi3k-akt-pathway
#3
Jin Zhang, Xuemei Zhang, Yingjie Liu, Zihao Su, Farman Ullah Dawar, Hong Dan, Yan He, Jian-Fang Gui, Jie Mei
Amino acid supplementation is an efficient and effective strategy to increase sperm quality. In our research, a comparative study was conducted to screen free amino acids to improve sperm motility, and we found that leucine was the most efficient one. Leucine treatment increases sperm motility depending on the activation of PI3K/Akt signaling pathway, while the chemical inhibitor of PI3K/Akt signal could reduce the amount of pAkt activated by leucine treatment. Moreover, leucine treatment improved the expression of P62 and LC3-II, substantially suppressed the autophagy process in zebrafish testis...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339018/nicotine-alleviates-chronic-stress-induced-anxiety-and-depressive-like-behavior-and-hippocampal-neuropathology-via-regulating-autophagy-signaling
#4
Xi Xiao, Xueliang Shang, Baohui Zhai, Hui Zhang, Tao Zhang
Recently, we reported that chronic nicotine significantly improved chronic stress-induced impairments of cognition and the hippocampal synaptic plasticity in mice, however, the underlying mechanism still needs to be explored. In the present study, 32 male C57BL/6 mice were divided into four groups: control (CON), stress (CUS), stress with chronic nicotine administration (CUS + Nic) and chronic nicotine administration (Nic). The anxiety-like behavior and neuropathological alteration of DG neurons were examined...
January 12, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29331805/synthesis-characterization-and-anticancer-activity-in%C3%A2-vitro-and-in%C3%A2-vivo-evaluation-of-an-iridium-iii-polypyridyl-complex
#5
Qiao-Yan Yi, Dan Wan, Bing Tang, Yang-Jie Wang, Wen-Yao Zhang, Fan Du, Miao He, Yun-Jun Liu
An iridium (III) complex [Ir(ppy)2(BDPIP)]PF6 (Ir-1) was reported to show high anticancer activity and may be used as a potent anticancer drug. In the current study, we designed and synthesized a novel iridium (III) complex and evaluated its potential inhibitory effect on the cancer cell growth in vitro and in vivo. This complex was found to display high cytotoxic activity in vitro and in vivo against A549 cell with a low IC50 value of 3.6 ± 0.3 μM and inhibiting percentage of tumor growth is 63.84% compared with the control...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29331753/an-iridium-iii-complex-as-potent-anticancer-agent-induces-apoptosis-and-autophagy-in-b16%C3%A2-cells-through-inhibition-of-the-akt-mtor-pathway
#6
Bing Tang, Dan Wan, Yang-Jie Wang, Qiao-Yan Yi, Bo-Hong Guo, Yun-Jun Liu
A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2-a:2',3'-c]phenazine) and its iridium(III) complex [Ir(ppy)2(THPDP)]PF6 (Ir-1) was synthesized and characterized by elemental analysis, IR, ESI-MS, 1H NMR and 13C NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca-109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0 ± 0.02, 1.4 ± 0...
December 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29328421/antitumor-activity-of-curcumin-by-modulation-of-apoptosis-and-autophagy-in-human-lung-cancer-a549-cells-through-inhibiting-pi3k-akt-mtor-pathway
#7
Furong Liu, Song Gao, Yuxuan Yang, Xiaodan Zhao, Yameng Fan, Wenxia Ma, Danrong Yang, Aimin Yang, Yan Yu
Curcumin is known to exhibit anticancer effects on various cancers with selective cytotoxicity in tumor cells. In the present study, the effects of curcumin‑induced multiple PCDs on human non‑small cell lung cancer (NSCLC) cells and the potential molecular mechanisms of apoptosis and autophagy triggered by curcumin via the PI3K/Akt/mTOR signaling pathway were explored, further confirmed by co‑culture of curcumin with mTOR blocker rapamycin and PI3K/Akt inhibitor LY294002. The anti‑proliferation effect of different stimulus was measured by MTT assay...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29317054/promising-horizon-to-alleviate-alzeheimer-s-disease-pathological-hallmarks-via-inhibiting-mtor-signaling-pathway-a-new-application-for-a-commonplace-analgesic
#8
Leila Pourtalebi Jahromi, Zahra Sasanipour, Amir Azadi
Alzheimer's disease (AD) is a very prevalent and burdensome disease of elderlies but albeit extensive studies, mechanisms underlying its pathology and consequently its definite treatment is ambiguous. Intra and extra-cellular aggregation of abnormal proteins and impaired autophagy machinery, two closely related events taking place in AD brains proposed to be directly controlled by mTOR signaling pathway. On the other hand, tramadol that is a very well tolerated opioid analgesic has been revealed to inhibit mTOR upstream controllers through interaction with specific types of muscarinic, serotonergic, nicotinic and NMDA receptors, although it seems to induce the opposite effect via µ-opioid receptor...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29316373/tanshinone-iia-induces-cell-death-via-beclin-1-dependent-autophagy-in-oral-squamous-cell-carcinoma-scc-9-cell-line
#9
Ye Qiu, Conghua Li, Qinhua Wang, Xingqi Zeng, Ping Ji
Tanshinone IIA (TAN) is one of the major functional compounds of Salvia miltiorrhiza Bunge and possesses the ability to suppress the growth of multiple cancer cell types via its apoptosis- and autophagy-inducing functions. In this study, the effect of TAN therapy on the survival of oral squamous cell carcinoma (OSCC) was evaluated, and the underlying mechanism involved in the treatment was investigated. Human oral squamous cell carcinoma cell SCC-9 was used for in vitro assays and induction in an OSCC xenograft mouse model...
January 6, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#10
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29296217/pharmacologic-characterization-of-shr8443-a-novel-dual-inhibitor-of-phosphatidylinositol-3-kinase-and-mammalian-target-of-rapamycin
#11
Chengying Xie, Xiangling Chen, Mingyue Zheng, Xiaohong Liu, Hongbin Wang, Liguang Lou
Dysregulation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs frequently in human cancer and contributes to resistance to antitumor therapy. Inhibition of key signaling proteins in this pathway therefore represents an attractive targeting strategy for cancer therapy. Here, we show that SHR8443, an imidazo [4,5-c] quinoline derivative, inhibited mammalian target of rapamycin (mTOR) kinase and PI3K, especially PI3Kα/δ/γ isoforms with picomolar potency, by binding to the ATP subunits of the respective enzymes...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290776/antitumor-activity-and-mechanism-of-a-reverse-transcriptase-inhibitor-dapivirine-in-glioblastoma
#12
Weiwen Liu, Xian-Lu Song, Shan-Chao Zhao, Minyi He, Hai Wang, Ziyang Chen, Wei Xiang, Guozhong Yi, Songtao Qi, Yawei Liu
ETHNOPHARMACOLOGICAL RELEVANCE: Dapivirine is one of reverse transcriptase inhibitors (RTIs). It is the prototype of diarylpyrimidines (DAPY), formerly known as TMC120 or DAPY R147681 (IUPAC name: 4- [[4-(2, 4, 6-trimethylphenyl) amino]-2-pyrimidinyl] amino]-benzonitrile; CAS no.244767-67-7). AIM: The purpose of this study is to investigate the antitumor activity of dapivirine, one of the RTIs, on U87 glioblastoma (GBM) cells in vitro and in vivo. MATERIALS AND METHODS: U87 GBM cells were cultured and treated with or without dapivirine...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29289836/brevilin-a-induces-apoptosis-and-autophagy-of-colon-adenocarcinoma-cell-ct26-via-mitochondrial-pathway-and-pi3k-akt-mtor-inactivation
#13
Pengtao You, Hezhen Wu, Meng Deng, Jingling Peng, Fangping Li, Yanfang Yang
Brevilin A is a sesquiterpene lactone isolated from Centipeda minima and possesses inhibitory effects on proliferation of various tumor cells. In this study, Brevilin A inhibitory effect on proliferation and its molecular mechanism of action were investigated both in vivo and in vitro in colon adenocarcinoma CT26 cells. The results indicated that the inhibitory effect of Brevilin A in CT26 proliferation was dose-dependent and this effect was due to apoptosis. Furthermore, Brevilin A increased ROS levels, decreased mitochondrial membrane potential (MMP) and induced apoptosis of CT26 cell in a dose-dependent manner...
December 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29282893/autophagy-novel-applications-of-nonsteroidal-anti-inflammatory-drugs-for-primary-cancer
#14
REVIEW
Chen Yu, Wei-Bing Li, Jun-Bao Liu, Jian-Wei Lu, Ji-Feng Feng
In eukaryotic cells, autophagy is a process associated with programmed cell death. During this process, cytoplasmic proteins and organelles are engulfed by double-membrane autophagosomes, which then fuse with lysosomes to form autolysosomes. These autolysosomes then degrade their contents to recycle the cellular components. Autophagy has been implicated in a wide variety of physiological and pathological processes that are closely related to tumorigenesis. In recent years, an increasing number of studies have indicated that nonsteroidal anti-inflammatory drugs, such as celecoxib, meloxicam, sulindac, aspirin, sildenafil, rofecoxib, and sodium salicylate, have diverse effects in cancer that are mediated by the autophagy pathway...
December 28, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29259984/mtor-dependent-cell-proliferation-in-the-brain
#15
REVIEW
Larisa Ryskalin, Gloria Lazzeri, Marina Flaibani, Francesca Biagioni, Stefano Gambardella, Alessandro Frati, Francesco Fornai
The mammalian Target of Rapamycin (mTOR) is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29244196/iron-overload-induces-g1-phase-arrest-and-autophagy-in-murine-preosteoblast-cells
#16
Wan-Jing Cen, Yi Feng, Shu-Shu Li, Wei-Liang Huang, Tao Zhang, Wu Zhang, Wei-Dong Kong, Jian-Wei Jiang
This study aimed to investigate the cell cycle arrest and autophagy induced by iron overload inMC3T3-E1 cells. MC3T3-E1 cells were cultured in different concentrations of ferric ammonium citrate (FAC), and Perls' Prussian blue reaction was used to detect the iron levels of the cells. CCK-8 assays were used to detect the growth of MC3T3-E1. The level of reactive oxygen species (ROS) within cells was investigated with DCFH-DA. PI staining was used to analyze the cell cycle distribution of MC3T3-E1 cells. Finally, the expression levels of cell cycle related proteins, autophagy related proteins, AKT, p38 MAPK, Stat3 and their downstream proteins were detected with western blot assays...
December 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29243061/neuroprotective-effect-of-curcumin-against-cerebral-ischemia-reperfusion-via-mediating-autophagy-and-inflammation
#17
Lifa Huang, Chengwei Chen, Xin Zhang, Xu Li, Zupeng Chen, Chao Yang, Xiaolong Liang, Guochong Zhu, Zhen Xu
Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R)...
December 15, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29228741/autophagy-inhibition-sensitizes-ly3023414-induced-anti-glioma-cell-activity-in-vitro-and-in-vivo
#18
Lan Zheng, Huanyin Li, Yanqing Mo, Gong Qi, Bin Liu, Jing Zhao
PI3K-AKT-mTOR signaling is a valuable treatment target for human glioma. LY3023414 is a novel, highly-potent and pan PI3K-AKT-mTOR inhibitor. Here, we show that LY3023414 efficiently inhibited survival and proliferation of primary and established human glioma cells. Meanwhile, apoptosis activation was observed in LY3023414-treated glioma cells. LY3023414 blocked AKT-mTOR activation in human glioma cells. Further studies show that LY3023414 induced feedback activation of autophagy in U251MG cells. On the other hand, autophagy inhibition via adding pharmacological inhibitors or silencing Beclin-1/ATG-5 significantly potentiated LY3023414-induced glioma cell apoptosis...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217185/selenizing-astragalus-polysaccharide-attenuates-pcv2-replication-promotion-caused-by-oxidative-stress-through-autophagy-inhibition-via-pi3k-akt-activation
#19
Dandan Liu, Jing Xu, Gang Qian, Mohammed Hamid, Fang Gan, Xingxiang Chen, Kehe Huang
Our previous studies have shown that oxidative stress could promote the porcine circovirus type 2 (PCV2) replication, and astragalus polysaccharide (APS)/selenium could suppress PCV2 replication. However, whether selenizing astragalus polysaccharide (sAPS) provides protection against oxidative stress-induced PCV2 replication promotion and the mechanism involved remain unclear. The present study aimed to explore the mechanism of the PCV2 replication promotion induced by oxidative stress and a novel pharmacotherapeutic approach involving the regulation of autophagy of sAPS...
December 4, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29212196/juglanin-inhibits-lung-cancer-by-regulation-of-apoptosis-ros-and-autophagy-induction
#20
Liang Chen, Ya-Qiong Xiong, Jing Xu, Ji-Peng Wang, Zi-Li Meng, Yong-Qing Hong
Juglanin (Jug) is obtained from the crude extract of Polygonum aviculare, exerting suppressive activity against cancer cell progression in vitro and in vivo. Juglanin administration causes apoptosis and reactive oxygen species (ROS) in different types of cells through regulating various signaling pathways. In our study, the effects of juglanin on non-small cell lung cancer were investigated. A significant role of juglanin in suppressing lung cancer growth was observed. Juglanin promoted apoptosis in lung cancer cells through increasing Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, which is regulated by TNF-related apoptosis-inducing ligand/Death receptors (TRAIL/DRs) relied on p53 activation...
November 7, 2017: Oncotarget
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