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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/27895729/celastrus-orbiculatus-extract-triggers-apoptosis-and-autophagy-via-pi3k-akt-mtor-inhibition-in-human-colorectal-cancer-cells
#1
Lin Yang, Yanqing Liu, Mei Wang, Yayun Qian, Xiaojun Dai, Yaodong Zhu, Jue Chen, Shiyu Guo, Tadashi Hisamitsu
Celastrus orbiculatus is used as a folk medicine in China for the treatment of numerous diseases. The ethyl acetate extract of Celastrus orbiculatus (COE) also displays a wide range of anti-cancer activities in the laboratory. However, the effectiveness of COE-induced autophagy and its mechanism of action in colorectal cancer cells have not been investigated thus far. The present study analyzed the effect of COE on HT-29 cell viability, apoptosis and autophagy using MTT assay, flow cytometry, transmission electron microscopy and western blotting...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27889779/tanshinone-iia-affects-autophagy-and-apoptosis-of-glioma-cells-by-inhibiting-phosphatidylinositol-3-kinase-akt-mammalian-target-of-rapamycin-signaling-pathway
#2
Lijuan Ding, Shudong Wang, Weiyao Wang, Peng Lv, Donghai Zhao, Feier Chen, Tianjiao Meng, Lihua Dong, Ling Qi
OBJECTIVE: To test the effects of Tanshinone IIA (Tan IIA) on cell viability, cycle, apoptosis, and autophagy of human glioma cell U251 by regulating phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signal pathway. METHODS: Tan IIA and PI3K agonist (740 Y-P) were used to treat glioma cells U251. MTT assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis and cell cycle. The expressions of apoptosis-related proteins (Bcl-2 and Bax), autophagy-related proteins (LC3B and Beclin 1) and PI3K/Akt/mTOR signal pathway-associated proteins (p-PI3K, p-Akt and p-mTOR) were evaluated by Western blotting...
November 26, 2016: Pharmacology
https://www.readbyqxmd.com/read/27886437/the-microrna-99-family-modulates-hepatitis-b-virus-replication-by-promoting-igf-1r-pi3k-akt-mtor-ulk1-signaling-induced-autophagy
#3
Yong Lin, Wanyu Deng, Jinke Pang, Thekla Kemper, Jing Hu, Jian Yin, Jiming Zhang, Mengji Lu
MicroRNAs (miRNAs) are small highly conserved noncoding RNAs that are widely expressed in multicellular organisms and participate in the regulation of various cellular processes including autophagy and viral replication. Evidently, miRNAs are able to modulate host gene expression and thereby inhibit or enhance hepatitis B virus (HBV) replication. The miR-99 family members are highly expressed in the liver. Interestingly, the plasma levels of miR-99 family in the peripheral blood correspond with HBV DNA loads...
November 25, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27885243/di-n-butyl-phthalate-induced-hypospadias-relates-to-autophagy-in-genital-tubercle-via-the-pi3k-akt-mtor-pathway
#4
Xiang Li, Jinhao Li, Ya Zhang, Yun Zhou
OBJECTIVE: To explore the mechanisms of hypospadias induced by in utero exposure to din-butyl phthalate (DBP). METHODS: Timed-pregnant Sprague-Dawley rats were administered 750 mg/kg of DBP by gavage from GD (gestation days) 13 to GD 18, whereas control group received corn oil. Genital tubercles (GTs) and blood samples were collected from male fetuses on GD 19. The serum testosterone concentration, apoptosis activity, autophagosomes and their related proteins (light chain 3 (LC3-I, LC3-II)), and sequestosomes (SQSTM1/p62) in the GTs were then measured...
November 22, 2016: Journal of Occupational Health
https://www.readbyqxmd.com/read/27882079/overexpression-of-caveolin-1-reduces-taxol-resistance-in-human-osteosarcoma-cells-by-attenuating-pi3k-akt-jnk-dependent-autophagy
#5
Jian Guan, Zhenchao Yuan, Juliang He, Zhenjie Wu, Bin Liu, Xiang Lin, Ligen Mo, Hao Mo
Caveolin-1 (CAV-1), which is an oncoprotein and a tumor suppressor, is highly expressed in normal osteoblasts. Although researchers have investigated its role in human osteosarcoma, the mechanism of caveolin-1 action in osteosarcoma remains unknown. In the present study, Saos-2 and U-2 OS cells were cultured with a continuous induction protocol of gradually increasing Taxol concentration for 6 months to establish drug-resistant cell lines. CAV-1 expression levels in osteosarcoma cells were detected via western blotting and quantitative polymerase chain reaction...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27879648/the-role-of-deoxycytidine-kinase-dck-in-radiation-induced-cell-death
#6
Rui Zhong, Rui Xin, Zongyan Chen, Nan Liang, Yang Liu, Shumei Ma, Xiaodong Liu
Deoxycytidine kinase (dCK) is a key enzyme in deoxyribonucleoside salvage and the anti-tumor activity for many nucleoside analogs. dCK is activated in response to ionizing radiation (IR)-induced DNA damage and it is phosphorylated on Serine 74 by the Ataxia-Telangiectasia Mutated (ATM) kinase in order to activate the cell cycle G2/M checkpoint. However, whether dCK plays a role in radiation-induced cell death is less clear. In this study, we genetically modified dCK expression by knocking down or expressing a WT (wild-type), S74A (abrogates phosphorylation) and S74E (mimics phosphorylation) of dCK...
November 21, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27878958/inhibition-of-orai1-mediated-ca-2-entry-enhances-chemosensitivity-of-hepg2-hepatocarcinoma-cells-to-5-fluorouracil
#7
Bao-Dong Tang, Xin Xia, Xiao-Fei Lv, Bei-Xin Yu, Jia-Ni Yuan, Xiao-Yi Mai, Jin-Yan Shang, Jia-Guo Zhou, Si-Jia Liang, Rui-Ping Pang
Increasing evidence supports that activation of store-operated Ca(2+) entry (SOCE) is implicated in the chemoresistance of cancer cells subjected to chemotherapy. However, the molecular mechanisms underlying chemoresistance are not well understood. In this study, we aim to investigate whether 5-FU induces hepatocarcinoma cell death through regulating Ca(2+) -dependent autophagy. [Ca(2+) ]i was measured using fura2/AM dye. Protein expression was determined by Western blotting and immunohistochemistry. We found that 5-fluorouracil (5-FU) induced autophagic cell death in HepG2 hepatocarcinoma cells by inhibiting PI3K/AKT/mTOR pathway...
November 23, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27866190/role-of-mcpip1-in-the-endothelial-mesenchymal-transition-induced-by-silica
#8
Jie Chao, Xingang Wang, Yuxia Zhang, Tiebing Zhu, Wei Zhang, Zewei Zhou, Jian Yang, Bing Han, Yusi Cheng, Xiaojie Tu, Honghong Yao
BACKGROUND: Silicosis is characterized by the accumulation of fibroblasts and the excessive deposition of extracellular matrix. Fibroblast generation via endothelial-mesenchymal transition (EndMT) is one process responsible for this accumulation of fibroblasts. However, the mechanisms underlying EndMT remain unknown. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to SiO2 (50 µg/cm2). Specific endothelial and mesenchymal markers were evaluated using immunofluorescence and western blot analysis...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27863407/induction-of-mitochondria-mediated-apoptosis-and-pi3k-akt-mtor-mediated-autophagy-by-aflatoxin-b2-in-hepatocytes-of-broilers
#9
Binlong Chen, Diyan Li, Miao Li, Sichen Li, Kenan Peng, Xian Shi, Lanyun Zhou, Pu Zhang, Zhongxian Xu, Huadong Yin, Yan Wang, Xiaoling Zhao
Aflatoxins have been shown to induce hepatotoxicity in animal models, but the effects of aflatoxin B2 (AFB2) on broiler hepatocytes is unclear. This study aimed to investigate the effects of AFB2 on apoptosis and autophagy to provide an experimental basis for understanding the mechanism of aflatoxin-induced hepatotoxicity. One hundred-twenty Cobb500 broilers were allocated to four groups and exposed to 0 mg/kg, 0.2 mg/kg, 0.4 mg/kg, and 0.8 mg/kg of AFB2 per day for 21 d. AFB2 exerted potent proapoptotic and proautophagic effects on hepatocytes, with increased numbers of apoptotic and autophagic hepatocytes...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863375/h2o2-treatment-or-serum-deprivation-induces-autophagy-and-apoptosis-in-naked-mole-rat-skin-fibroblasts-by-inhibiting-the-pi3k-akt-signaling-pathway
#10
Shanmin Zhao, Li Li, Shiyong Wang, Chenlin Yu, Bang Xiao, Lifang Lin, Wei Cong, Jishuai Cheng, Wenjing Yang, Wei Sun, Shufang Cui
Naked mole-rats (NMR; Heterocephalus glaber) display extreme longevity and resistance to cancer. Here, we examined whether autophagy contributes to the longevity of NMRs by assessing the effects of the PI3K/Akt pathway inhibitor LY294002 and the autophagy inhibitor chloroquine (CQ) on autophagy and apoptosis in NMR skin fibroblasts. Serum starvation, H2O2 treatment, and LY294002 treatment all increased the LC3-II/LC3-I ratio and numbers of double-membraned autophagosomes and autophagic vacuoles, and decreased levels of p70S6K, p-AktSer473, and p-AktThr308...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863372/the-fucosylated-cd147-enhances-the-autophagy-in-epithelial-ovarian-cancer-cells
#11
Zhenhua Hu, Mingbo Cai, Lu Deng, Liancheng Zhu, Jian Gao, Mingzi Tan, Juanjuan Liu, Bei Lin
Autophagy is modulated by multiple factors including CD147, but little is know about the effects and mechanism by which the modification of CD147 by Lewis y antigen regulates autophagy of ovarian cancer cell. Here, we reported that Lewis y antigen can promote basic autophagy activity and restrain autophagic cell death in ovarian cancer cells. Furthermore, human whole genome expression profile microarrays and massage pathway analysis revealed that during early stages of autophagy in ovarian cancer cells with highly expressing Lewis y antigen, PI3K/Akt-mTOR activity was reduced, in contrast, the PI3K/Akt-mTOR signaling pathway was activated as the length of amino acid deprivation increased, which inhibited eIF4G2 expression, further decreased the transcription of autophagy-related genes, suppressed autophagic cell death...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832966/nonylphenol-induced-apoptosis-and-autophagy-involving-the-akt-mtor-pathway-in-prepubertal-sprague-dawley-male-rats-in-vivo-and-in-vitro
#12
Wenting Huang, Chao Quan, Peng Duan, Sha Tang, Wei Chen, Kedi Yang
This research explores the detrimental effect of nonylphenol (NP) to prepubertal Sprague-Dawley male rats in vivo and in vitro. Herein, forty-two 3-week-old rats were randomly divided into six groups, which were treated with NP (0, NAC, 25, 50, 100, 100+NACmg/kg/2d for 30 consecutive days) by intraperitoneal injection. NP induced a reduction in testosterone (15.58%, 17.23%, 13.38% in 25, 50, 100mg/kg group, respectively), triggered apoptosis related to oxidative stress, and disturbed mRNA and/or protein levels of PI3K, PTEN, PDK1, p-Akt, p-mTOR, p70S6K, caspase-3, LC3B...
December 12, 2016: Toxicology
https://www.readbyqxmd.com/read/27830018/insulin-like-growth-factor-1-antagonizes-lumbar-disc-degeneration-through-enhanced-autophagy
#13
Zuo-Qing Liu, Shan Zhao, Wen-Qin Fu
Autophagy has been shown to antagonize the development of Lumbar disc degeneration (LDD), whereas the molecular regulation of autophagy is unknown. We recently reported a potential role of Insulin-like growth factor 1 receptor (IGF1R)/phosphatidylinositol-3 kinase (PI3k)/Akt signaling in the initiation and progression of LDD. Here, we studied the effects of IGF1R signaling on disc cell autophagy. We showed a correction of activation of IGF1R and disc cell autophagy in the resected discs in LDD patients. In vitro, activation of IGF1R signaling antagonized the decreases in cell viability of human disc cells, HNPSV, through suppression of apoptosis and enhancement of autophagy...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27821800/synergistic-effects-of-selective-inhibitors-targeting-the-pi3k-akt-mtor-pathway-or-nup214-abl1-fusion-protein-in-human-acute-lymphoblastic-leukemia
#14
Carolina Simioni, Simona Ultimo, Alberto M Martelli, Giorgio Zauli, Daniela Milani, James A McCubrey, Silvano Capitani, Luca M Neri
Philadelphia chromosome-positive (Ph+) Acute Lymphoblastic Leukemia (ALL) accounts for 25-30% of adult ALL and its incidence increases with age in adults >40 years old. Irrespective of age, the ABL1 fusion genes are markers of poor prognosis and amplification of the NUP214-ABL1 oncogene can be detected mainly in patients with T-ALL. T cell malignancies harboring the ABL1 fusion genes are sensitive to many cytotoxic agents, but up to date complete remissions have not been achieved. The PI3K/Akt/mTOR signaling pathway is often activated in leukemias and plays a crucial role in leukemogenesis...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815218/oxyresveratrol-activates-parallel-apoptotic-and-autophagic-cell-death-pathways-in-neuroblastoma-cells
#15
Md Ataur Rahman, Kausik Bishayee, Ali Sadra, Sung-Oh Huh
BACKGROUND: Drug resistance from apoptosis is a challenging issue with different cancer types, and there is an interest in identifying other means of inducing cytotoxicity. Here, treatment of neuroblastoma cells with oxyresveratrol (OXYRES), a natural antioxidant, led to dose-dependent cell death and increased autophagic flux along with activation of caspase-dependent apoptosis. METHODS: For cell viability, we performed the CCK-8 assay. Protein expression changes were with Western blot and immunocytochemistry...
November 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27807764/mice-lacking-myotubularin-related-protein-14-show-accelerated-high-fat-diet-induced-lipid-accumulation-and-inflammation
#16
Lv Yin, Peng Yong-Bo, Yu Meng-Fei, Chen Weiwei, Zhao Ping, Xue Lu, Ma Li-Qun, Cai Congli, Liu Qing-Hua, Shen Jinhua
The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD...
November 2, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27805285/survivin-inhibitor-ym155-induces-mitochondrial-dysfunction-autophagy-dna-damage-and-apoptosis-in-bcl-xl-silenced-glioma-cell-lines
#17
Esther P Jane, Daniel R Premkumar, Philip A Sutera, Jonathon M Cavaleri, Ian F Pollack
Because the anti-apoptotic protein Bcl-xL is overexpressed in glioma, one might expect that inhibiting or silencing this gene would promote tumor cell killing. However, our studies have shown that this approach has limited independent activity, but may tip the balance in favor of apoptosis induction in response to other therapeutic interventions. To address this issue, we performed a pharmacological screen using a panel of signaling inhibitors and chemotherapeutic agents in Bcl-xL silenced cells. Although limited apoptosis induction was observed with a series of inhibitors for receptor tyrosine kinases, PKC inhibitors, Src family members, JAK/STAT, histone deacetylase, the PI3K/Akt/mTOR pathway, MAP kinase, CDK, heat shock proteins, proteasomal processing, and various conventional chemotherapeutic agents, we observed a dramatic potentiation of apoptosis in Bcl-xL silenced cells with the survivin inhibitor, YM155...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27788478/the-effect-of-jak2-knockout-on-inhibition-of-liver-tumor-growth-by-inducing-apoptosis-autophagy-and-anti-proliferation-via-stats-and-pi3k-akt-signaling-pathways
#18
Ying Xu, Sheng-Xiang Lv
Liver cancer is a leading cause of cancer death, making it as the second most common cause for death from cancer globally. Though many studies before have explored a lot for liver cancer prevention and treatment, there are still a lot far from to know based on the molecular mechanisms. Janus kinase 2 (JAK2) has been reported to play an essential role in the progression of apoptosis, autophagy and proliferation for cells. Therefore, we were aimed to investigate the underlying mechanisms by which JAK2 performed its role in ameliorating liver cancer...
October 24, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27786281/synthesis-and-biological-evaluation-of-matrine-derivatives-containing-benzo-%C3%AE-pyrone-structure-as-potent-anti-lung-cancer-agents
#19
Lichuan Wu, Guizhen Wang, Shuaibing Liu, Jinrui Wei, Sen Zhang, Ming Li, Guangbiao Zhou, Lisheng Wang
Matrine, an active component of root extracts from Sophora flavescens Ait, is the main chemical ingredient of Fufang Kushen injection which was approved by Chinese FDA (CFDA) in 1995 as an anticancer drug to treat non-small cell lung cancer and liver cancer in combination with other anticancer drugs. Owning to its druggable potential, matrine is considered as an ideal lead compound for modification. We delineate herein the synthesis and anticancer effects of 17 matrine derivatives bearing benzo-α-pyrone structures...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27785026/amorphous-silica-nanoparticles-trigger-vascular-endothelial-cell-injury-through-apoptosis-and-autophagy-via-reactive-oxygen-species-mediated-mapk-bcl-2-and-pi3k-akt-mtor-signaling
#20
Caixia Guo, Man Yang, Li Jing, Ji Wang, Yang Yu, Yang Li, Junchao Duan, Xianqing Zhou, Yanbo Li, Zhiwei Sun
Environmental exposure to silica nanoparticles (SiNPs) is inevitable due to their widespread application in industrial, commercial, and biomedical fields. In recent years, most investigators focus on the evaluation of cardiovascular effects of SiNPs in vivo and in vitro. Endothelial injury and dysfunction is now hypothesized to be a dominant mechanism in the development of cardiovascular diseases. This study aimed to explore interaction of SiNPs with endothelial cells, and extensively investigate the exact effects of reactive oxygen species (ROS) on the signaling molecules and cytotoxicity involved in SiNPs-induced endothelial injury...
2016: International Journal of Nanomedicine
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