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mtor protein, human

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https://www.readbyqxmd.com/read/27903983/dyrk1b-blocks-canonical-and-promotes-non-canonical-hedgehog-signaling-through-activation-of-the-mtor-akt-pathway
#1
Rajeev Singh, Pavan Kumar Dhanyamraju, Matthias Lauth
Hedgehog (Hh) signaling plays important roles in embryonic development and in tumor formation. Apart from the well-established stimulation of the GLI family of transcription factors, Hh ligands promote the phosphorylation and activation of mTOR and AKT kinases, yet the molecular mechanism underlying these processes are unknown. Here, we identify the DYRK1B kinase as a mediator between Hh signaling and mTOR/AKT activation. In fibroblasts, Hh signaling induces DYRK1B protein expression, resulting in activation of the mTOR/AKT kinase signaling arm...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902464/expression-of-rab1a-is-upregulated-in-human-lung-cancer-and-associated-with-tumor-size-and-t-stage
#2
Xinxin Wang, Feng Liu, Xiaoyu Qin, Tinglei Huang, Bo Huang, Yanjie Zhang, Bin Jiang
Rab1A expression is associated with malignant phenotypes in several human tumors; however, the role of Rab1A in lung cancer is still unclear. In this study, we attempted to establish the role of Rab1A in major human lung cancer subtypes. Rab1A expression in different histological types of human lung cancer was analyzed in lung cancer tissues with paired adjacent noncancerous tissues and a large panel of lung cancer cell lines. The effect of Rab1A expression on multiple cancer-associated signaling pathways was also examined...
November 29, 2016: Aging
https://www.readbyqxmd.com/read/27900044/plumbagin-inhibits-cell-proliferation-and-promotes-apoptosis-in-multiple-myeloma-cells-through-inhibition-of-the-pi3k-akt-mtor-pathway
#3
Hongwei Wu, Xiaozhen Dai, Enren Wang
Plumbagin is the primary component of the traditional Chinese medicine Baihua Dan, and possesses anti-infection and anticancer effects with the ability to enhance the sensitivity of tumor cells to radiation therapy. The present study aimed to investigate the potential anticancer effect and mechanism of plumbagin on multiple myeloma (MM) cells. Human MM OPM1 cells were treated with plumbagin, and its impact on cell viability, cytotoxicity, apoptosis and caspase-3 activity was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase leakage, flow cytometry and colorimetric assays...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899988/mtor-downstream-effectors-4ebp1-and-eif4e-are-overexpressed-and-associated-with-hpv-status-in-precancerous-lesions-and-carcinomas-of-the-uterine-cervix
#4
Aristidis Asimomytis, Maria Karanikou, Alexander Rodolakis, Anna Vaiopoulou, Paraskevi Tsetsa, George Creatsas, Theodoros Stefos, Aristidis Antsaklis, Efstratios Patsouris, George Z Rassidakis
The present study aims to investigate the expression levels of two critical mammalian target of rapamycin (mTOR) downstream effectors, 4E binding protein 1 (4EBP1) and eukaryotic initiation factor 4E (eIF4E) proteins, in precancerous squamous intraepithelial lesions and cancer of the uterine cervix, and their association with human papilloma virus (HPV) infection status. Uterine cervical biopsies from 73 patients were obtained, including 40 fresh-frozen samples and 42 archival formalin-fixed, paraffin-embedded tissue specimens...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27897164/hmgb1-mediated-autophagy-decreases-sensitivity-to-oxymatrine-in-sw982-human-synovial-sarcoma-cells
#5
Yongsong Cai, Peng Xu, Le Yang, Ke Xu, Jialin Zhu, Xiaoqing Wu, Congshan Jiang, Qiling Yuan, Bo Wang, Yuanbo Li, Yusheng Qiu
Oxymatrine (OMT) is a type of alkaloid extracted from a traditional Chinese medicinal herb, Sophora flavescens. Although the antitumor activities of OMT have been observed in various cancers, there are no reports regarding the effects of OMT on human synovial sarcoma. In the present study, we analyzed the antitumor activities of OMT in SW982 human synovial sarcoma cells and determine whether high mobility group box protein 1 (HMGB1)-mediated autophagy was associated with its therapeutic effects. We found that OMT exhibited antitumor activity in SW982 cells and facilitated increases in autophagy...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895729/celastrus-orbiculatus-extract-triggers-apoptosis-and-autophagy-via-pi3k-akt-mtor-inhibition-in-human-colorectal-cancer-cells
#6
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
#7
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/27881463/sestrin-3-modulation-is-essential-for-therapeutic-efficacy-of-cucurbitacin-b-in-lung-cancer-cells
#8
Naghma Khan, Farah Jajeh, Mohammad Imran Khan, Eiman Mukhtar, Sameh M Shabana, Hasan Mukhtar
Many purified compounds from dietary sources have been investigated for their anticancer activities. The main issue with most agents is their effectiveness at high doses which generally could not be delivered to humans through dietary consumption. Here, we observed that cucurbitacin B, a tetracyclic triterpenoid present in pumpkins, gourds and squashes, exhibits antiproliferative effects on human non-small cell lung cancer (NSCLC) cells at nanomolar concentrations. Treatment with cucurbitacin B (0.2-0.6 μM; 24 h) was found to result in decrease in the viability of EGFR-wild type (A549 and H1792) and EGFR-mutant lung cancer cells (H1650 and H1975) and reduction in cell-colonies but had only minimal effect on normal human bronchial epithelial cells...
November 23, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27880045/koelreuteria-formosana-extract-induces-growth-inhibition-and-cell-death-in-human-colon-carcinoma-cells-via-g2-m-arrest-and-lc3-ii-activation-dependent-autophagy
#9
Chi-Ting Horng, Yueh-Jung Wu, Pei-Ni Chen, Shu-Chen Chu, Chun-Miao Tsai, Yih-Shou Hsieh
Autophagy is a self-destructive process that degrades cytoplasmic constituents. In our previous study, Koelreuteria formosana ethanolic extract (KFEE), which is obtained from natural plants endemic to Taiwan, has inhibited cell metastasis in renal carcinoma cells. However, the anticancer effects of KFEE on colon cancer remain unclear. In this study, KFEE exerted a strong cytotoxic effect on DLD-1 and COLO 205 human colorectal cancer cell lines. KFEE effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with downregulaton of cyclin E, cyclin B and cdc25C and upregulation of p21, and induced cell death by activating autophagy but did not cause apoptotic cell death...
November 23, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27878292/bmi-1-interacts-with-smek1-and-inactivates-smek1-induced-apoptotic-cell-death
#10
Boh-Ram Kim, Youngjoo Kwon, Seung Bae Rho
The B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) protein is activated in various types of tumors and associated with cancer development and tumor progression. However, the working role of BMI-1 in cellular signaling is not understood completely. In this study, we revealed one possible biologic mechanism of BMI-1 in cancer progression in vitro using a human ovarian tumor cell system. Suppressor of MEK1 (sMEK1), a pivotal regulator involved in the cellular biological response mechanism, was identified as a BMI-1-binding protein...
November 21, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27871897/sauchinone-exerts-anticancer-effects-by-targeting-ampk-signaling-in-hepatocellular-carcinoma-cells
#11
Young Woo Kim, Eun Jeong Jang, Chang-Hyun Kim, Ju-Hee Lee
Sauchinone is a pharmacologically active compound isolated from Saururus chinensis, which has been used as a traditional Oriental medicine to treat fever, jaundice, and various inflammatory diseases. In this study, we investigated the effect of sauchinone against hepatocellular carcinoma (HCC) and sought to elucidate the mechanism involved. Cell viability was measured by an MTT assay. Cell cycle distributions and the mitochondrial membrane potential were analyzed using flow cytometry. Cell death was analyzed by annexin V assay, 4',6-diamidino-2-phenylindole staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay...
November 18, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27863441/sulforaphane-inhibits-proliferation-and-invasive-activity-of-everolimus-resistant-kidney-cancer-cells-in-vitro
#12
Eva Juengel, Sebastian Maxeiner, Jochen Rutz, Saira Justin, Frederik Roos, Wael Khoder, Igor Tsaur, Karen Nelson, Wolf O Bechstein, Axel Haferkamp, Roman A Blaheta
Although the mechanistic target of rapamycin (mTOR) inhibitor, everolimus, has improved the outcome of patients with renal cell carcinoma (RCC), improvement is temporary due to the development of drug resistance. Since many patients encountering resistance turn to alternative/complementary treatment options, an investigation was initiated to evaluate whether the natural compound, sulforaphane (SFN), influences growth and invasive activity of everolimus-resistant (RCCres) compared to everolimus-sensitive (RCCpar) RCC cell lines in vitro...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863387/aberrant-overexpression-of-adar1-promotes-gastric-cancer-progression-by-activating-mtor-p70s6k-signaling
#13
Ning Dou, Shijun Yu, Xiaojuan Ye, Dong Yang, Yandong Li, Yong Gao
ADAR1, one of adenosine deaminases acting on RNA, modulates RNA transcripts through converting adenosine (A) to inosine (I) by deamination. Emerging evidence has implicated that ADAR1 plays an important role in a few of human cancers, however, its expression and physiological significance in gastric cancer remain undefined. In the present study, we demonstrated that ADAR1 was frequently overexpressed in gastric cancer samples by quantitative real-time PCR analysis. In a gastric cancer tissue microarray, ADAR1 staining was closely correlated with tumor stage (P < 0...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863372/the-fucosylated-cd147-enhances-the-autophagy-in-epithelial-ovarian-cancer-cells
#14
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/27860187/autophagy-activated-by-tuberin-mtor-p70s6k-suppression-is-a-protective-mechanism-against-local-anaesthetics-neurotoxicity
#15
Jingwei Xiong, Qiuyue Kong, Leyang Dai, He Ma, Xiaofei Cao, Li Liu, Zhengnian Ding
The local anaesthetics (LAs) are widely used for peripheral nerve blocks, epidural anaesthesia, spinal anaesthesia and pain management. However, exposure to LAs for long duration or at high dosage can provoke potential neuronal damages. Autophagy is an intracellular bulk degradation process for proteins and organelles. However, both the effects of LAs on autophagy in neuronal cells and the effects of autophagy on LAs neurotoxicity are not clear. To answer these questions, both lipid LAs (procaine and tetracaine) and amide LAs (bupivacaine, lidocaine and ropivacaine) were administrated to human neuroblastoma SH-SY5Y cells...
November 15, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27857021/effects-and-mechanisms-of-metformin-on-the-proliferation-of-esophageal-cancer-cells-in-vitro-and-in-vivo
#16
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27853236/regulation-of-sirt1-nrf2-tnf-%C3%AE-signaling-pathway-by-luteolin-is-critical-to-attenuate-acute-mercuric-chloride-exposure-induced-hepatotoxicity
#17
Daqian Yang, Xiao Tan, Zhanjun Lv, Biying Liu, Ruiqi Baiyun, Jingjing Lu, Zhigang Zhang
Inorganic mercury, though a key component of pediatric vaccines, is an environmental toxicant threatening human health via accumulating oxidative stress in part. Luteolin has been of great interest because of its antiinflammatory, anticarcinogenic and antioxidative effects. Here we hypothesized that luteolin would attenuate hepatotoxicity induced by acute inorganic mercury exposure. Kunming mice were treated with luteolin (100 mg/kg) 24 h after administration of 4 mg/kg mercuric chloride (HgCl2). The results showed that luteolin ameliorated HgCl2 induced anemia and hepatotoxicity, regulating radical oxygen species (ROS) production and hepatocyte viability in vitro and oxidative stress and apoptosis in vivo...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27849558/identification-of-a-fluorescent-small-molecule-enhancer-for-therapeutic-autophagy-in-colorectal-cancer-by-targeting-mitochondrial-protein-translocase-tim44
#18
Yinghui Huang, Jie Zhou, Shenglin Luo, Yang Wang, Jintao He, Peng Luo, Zelin Chen, Tao Liu, Xu Tan, Juanjuan Ou, Hongming Miao, Houjie Liang, Chunmeng Shi
OBJECTIVE: As the modulation of autophagic processes can be therapeutically beneficial to cancer treatment, the identification of novel autophagic enhancers is highly anticipated. However, current autophagy-inducing anticancer agents exert undesired side effects owing to their non-specific biodistribution in off-target tissues. This study aims to develop a multifunctional agent to integrate cancer targeting, imaging and therapy and to investigate its mechanism. DESIGN: A series of mitochondria-targeting near-infrared (NIR) fluorophores were synthesised, screened and identified for their autophagy-enhancing activity...
November 14, 2016: Gut
https://www.readbyqxmd.com/read/27829579/curcumin-suppresses-epithelial-mesenchymal-transition-of-renal-tubular-epithelial-cells-through-the-inhibition-of-akt-mtor-pathway
#19
Fang-Qiang Zhu, Min-Jia Chen, Ming Zhu, Rong-Seng Zhao, Wei Qiu, Xiang Xu, Hong Liu, Hong-Wen Zhao, Rong-Jie Yu, Xiong-Fei Wu, Keqin Zhang, Hong Huang
Curcumin has exhibited a protective effect against development of renal fibrosis in animal models, however, its underlying molecular mechanisms are largely unclear. Therefore, we investigated the anti-fibrosis effects of curcumin in TGF-β1-induced epithelial-to-mesenchymal transition (EMT), and the mechanism by which it mediates the PI3K/Akt pathway. Human kidney tubular epithelial cells (HKCs) were treated with TGF-β1 or curcumin alone, or TGF-β1 in combination with curcumin. The effect of curcumin on cell proliferation was measured by MTT assay...
November 8, 2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27825169/inhibition-of-mdm2-re-sensitizes-rapamycin-resistant-renal-cancer-cells-via-the-activation-of-p53
#20
Xin Tian, Shundong Dai, Jing Sun, Shenyi Jiang, Chengguang Sui, Fandong Meng, Yan Li, Liye Fu, Tao Jiang, Yang Wang, Jia Su, Youhong Jiang
BACKGROUND/AIMS: Rapamycin is a potential anti-cancer agent, which modulates the activity of mTOR, a key regulator of cell growth and proliferation. However, several types of cancer cells are resistant to the anti-proliferative effects of rapamycin. In this study, we report a MDM2/p53-mediated rapamycin resistance in human renal cancer cells. METHODS: Trypan blue exclusion tests were used to determine the cell viability. Changes in mRNA and protein expression were measured using real-time PCR and western blot, respectively...
2016: Cellular Physiology and Biochemistry
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