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mtor protein, human

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https://www.readbyqxmd.com/read/29048654/telmisartan-inhibits-hepatocellular-carcinoma-cell-proliferation-in-vitro-by-inducing-cell-cycle-arrest
#1
Kyoko Oura, Tomoko Tadokoro, Shintaro Fujihara, Asahiro Morishita, Taiga Chiyo, Eri Samukawa, Yoshimi Yamana, Koji Fujita, Teppei Sakamoto, Takako Nomura, Hirohito Yoneyama, Hideki Kobara, Hirohito Mori, Hisakazu Iwama, Keiichi Okano, Yasuyuki Suzuki, Tsutomu Masaki
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related death. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB) that might inhibit cancer cell proliferation, but the mechanisms through which telmisartan affects various cancers remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human HCC and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on HCC cells using the HLF, HLE, HepG2, HuH-7 and PLC/PRF/5 cell lines...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048631/autophagy-induction-enhances-tetrandrine-induced-apoptosis-via-the-ampk-mtor-pathway-in-human-bladder-cancer-cells
#2
Bo Kou, Wei Liu, Xu Xu, Yang Yang, Qiuyue Yi, Fengwei Guo, Jianpeng Li, Jinsong Zhou, Qingshan Kou
Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra is a traditional Chinese medicine and exerts anticancer capacity in various types of cancers. Previous studies have shown that tetrandrine induces apoptosis in bladder cancer cells via activation of the caspase cascade. However, the underlying mechanism has not yet been reported. Autophagy is a cellular process involved in the degradation of broken proteins and aging organelles to maintain homeostasis. Recent studies indicate that autophagy is implicated in cancer therapy...
September 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29041842/identifying-novel-small-molecule-antagonists-for-mlst8-protein-using-computational-approaches
#3
Tuleshwori Devi Sapam, Anbumani Velmurugan Ilavarasi, Bhagath Kumar Palaka, Elakkiya Elumalai, Nirmala Devi Kanika, Dinakara Rao Ampasala
Mammalian lethal with SEC13 protein 8 (mLST8), is an indispensable protein subunit of mammalian target of rapamycin (mTOR) signaling pathway that interacts with the kinase domain of mTOR protein, thereby stabilizing its active site. Experimental studies reported the over expression of mLST8 in human colon and prostate cancers by activation of both mTORC1/2 complexes and subsequent downstream substrates leading to tumor progression. Considering its role, targeting mLST8 protein would be a therapeutic approach against tumor progression in colon and prostate cancers...
October 17, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/29040365/role-of-the-akt-mtor-signaling-pathway-in-human-papillomavirus-associated-nasal-and-sinonasal-inverted-papilloma
#4
Yongliang Liu, Lihua Duan, Jie Tian, Daoliang Song, Min Zhang, Shenlin Zhao, Zhaofu Yin, Xinxin Xiang, Xuezhong Li
Nasal and sinonasal inverted papilloma (NSIP) is a benign tumor in which surface epithelial cells grow downward into the underlying supportive tissue with varying degrees of metaplasia. Human papillomavirus (HPV) has been proposed as the causal agent in the pathogenesis of this disease. Many studies have shown that HPV can activate the Akt/mechanistic target of rapamycin (mTOR) signaling pathway, but the role of this pathway in HPV-associated NSIP is largely unknown. In this study, we enrolled 40 control tissue samples and 80 NSIP tissue samples...
October 13, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29031066/serendipitous-discovery-of-potent-human-head-and-neck-squamous-cell-carcinoma-anti-cancer-molecules-a-fortunate-failure-of-a-rational-molecular-design
#5
Chiara Zagni, Venerando Pistarà, Luciana A Oliveira, Rogerio M Castilho, Giovanni Romeo, Ugo Chiacchio, Antonio Rescifina
Histone deacetylase inhibitors (HDACis) play an important role as valuable drugs targeted to cancer therapy: several HDACis are currently being tested in clinical trials. Two new potential HDACis 1a and 1d, characterized by the presence of a biphenyl-4-sulfonamide group as a connection unit between the N-{4-[(E)-(2-formylhydrazinylidene)methyl]-3-hydroxyphenyl} and the 2-hydroxy-N-(trifluoroacetyl)benzamide moiety, respectively, as two zinc-binding group (ZBG), have been designed, synthesized and tested for their biological activity...
October 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29030491/autophagy-is-activated-in-the-ovarian-tissue-of-polycystic-ovary-syndrome
#6
Da Li, Yue You, Fang-Fang Bi, Tie-Ning Zhang, Jiao Jiao, Tian-Ren Wang, Yi-Ming Zhou, Zi-Qi Shen, Xiu-Xia Wang, Qing Yang
The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased...
October 13, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29029434/silencing-protein-kinase-c-%C3%AE-by-microrna-25-5p-activates-ampk-signaling-and-inhibits-colorectal-cancer-cell-proliferation
#7
Shihu Zhang, Yiyang Zhang, Qing Cheng, Zhaoqun Ma, Guanwen Gong, Zhengming Deng, Kun Xu, Gaoyuan Wang, Yousong Wei, Xiaoping Zou
Developing novel strategies against human colorectal cancer (CRC) cells is needed. Activation of AMP-activated protein kinase (AMPK) could possibly inhibit CRC cells. Protein kinase C ζ (PKCζ) is an AMPK negative regulator. Here we found that PKCζ expression was significantly elevated in human colon cancer tissues and CRC cells. PKCζ upregulation was correlated with AMPK in-activation and mTOR complex 1 (mTORC1) over-activation. Reversely, PKCζ shRNA knockdown activated AMPK signaling and inhibited HT-29 cell proliferation...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29021233/divergent-activity-of-pseudogene-ptenp1-in-er-positive-and-negative-breast-cancer
#8
Synnøve Yndestad, Eilin Austreid, Kai Ove Skaftnesmo, Per Eystein Lønning, Hans P Eikesdal
Transcripts derived from the PTEN pseudogene (PTENP1) function as decoys to adsorb microRNAs (miRs) targeting the PTEN tumor suppressor for degradation, and PTENP1 upregulation is known to inhibit growth in preclinical cancer models. Here, PTENP1 3'UTR transduction influences PTEN, AKT/mTOR signaling, and tumor progression in estrogen receptor (ER)-positive and negative breast cancer cells. PTENP1 upregulation decreases PTEN gene expression in the ER-positive MCF7 and T47D human breast carcinoma cells and accelerates MCF7 tumor growth in vivo...
October 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29018148/suppression-of-cyp1-members-of-the-ahr-response-by-pathogen-associated-molecular-patterns
#9
Adam G Peres, Robert Zamboni, Irah L King, Joaquín Madrenas
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that triggers a broad response, which includes the regulation of proinflammatory cytokine production by monocytes and macrophages. AHR is negatively regulated by a set of genes that it transcriptionally activates, including the AHR repressor (Ahrr) and the cytochrome P450 1 (Cyp1) family, which are critical for preventing exacerbated AHR activity. An imbalance in these regulatory mechanisms has been shown to cause severe defects in lymphoid cells...
October 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28990932/uromodulin-p-cys147trp-mutation-drives-kidney-disease-by-activating-er-stress-and-apoptosis
#10
Bryce G Johnson, Lan T Dang, Graham Marsh, Allie M Roach, Zebulon G Levine, Anthony Monti, Deepak Reyon, Lionel Feigenbaum, Jeremy S Duffield
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks...
October 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28990042/hydroxytyrosol-contributes-to-cell-proliferation-and-inhibits-apoptosis-in-pulsed-electromagnetic-fields-treated-human-umbilical-vein-endothelial-cells-in-vitro
#11
Yong Cheng, Zhiwei Qu, Ximeng Fu, Qi Jiang, Jianfeng Fei
A variety of pulsed electromagnetic fields (PEMFs) have been experimentally and clinically used in an effort to promote wound healing, although the mechanisms involved remain unknown. The aim of the present study was to investigate the action of a novel protocol of co‑treatment with PEMFs and hydroxytyrosol (HTY) on the proliferation and differentiation potential of human umbilical vein endothelial cells (HUVECs). The HUVECs were assigned randomly into three groups: Control, PEMF‑treated and PEMF + HT‑treated...
October 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28988530/hyperexpression-of-integrin-%C3%AE-5%C3%AE-1-promotes-resistance-of-mcf-7-human-breast-carcinoma-cells-to-doxorubicin-via-erk-protein-kinase-down-regulation
#12
G E Morozevich, N I Kozlova, O Y Susova, A Y Lupatov, A E Berman
In MCF-7 human breast carcinoma cells, α5β1 integrin hyperexpression, which was accomplished by transduction of a full-length α5 integrin cDNA, increased by about 50-70% the number of cells, survived during 48-72 h cell treatment with doxorubicin. Up-regulation of α5β1 reduced the level of the apoptogenic p53 protein and p21 cell cycle inhibitor, but enhanced the activity of Akt and mTOR protein kinases. In addition to these findings, we observed a significant decrease in the activity of both isoforms of phosphokinase Erk1/2, which is known to play a key role in cell viability pathways, including pathways alleviating stress damages caused by distinct antitumor drugs...
September 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28987947/mir-206-inhibits-head-and-neck-squamous-cell-carcinoma-cell-progression-by-targeting-hdac6-via-pten-akt-mtor-pathway
#13
Fangzhou Liu, Xiaotong Zhao, Yichun Qian, Jia Zhang, Yuan Zhang, Rong Yin
As a kind of endogenous noncoding small RNA, microRNA (miRNA) plays important roles of regulation to various physiological functions, while its affections on senescence of human Head and neck squamous cell carcinoma (HNSCC) are still unknown. The objective of this study was to investigate the effect of miR-206 in HNSCC tissues, adjacent normal tissues and cell lines, and explore its biological functions in HNSCC. In our study, the level of miR-206 in HNSCC tissues and adjacent normal tissues was detected via real-time qPCR...
October 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28987943/a-standardized-extract-of-butea-monosperma-lam-flowers-suppresses-the-il-1%C3%AE-induced-expression-of-il-6-and-matrix-metalloproteases-by-activating-autophagy-in-human-osteoarthritis-chondrocytes
#14
Mohammad Y Ansari, Nazir M Khan, Tariq M Haqqi
BACKGROUND/OBJECTIVE: Osteoarthritis (OA) is a leading cause of joint dysfunction, disability and poor quality of life in the affected population. The underlying mechanism of joint dysfunction involves increased oxidative stress, inflammation, high levels of cartilage extracellular matrix degrading proteases and decline in autophagy-a mechanism of cellular defense. There is no disease modifying therapies currently available for OA. Different parts of the Butea monosperma (Lam.) plant have widely been used in the traditional Indian Ayurvedic medicine system for the treatment of various human diseases including inflammatory conditions...
October 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28987049/downregulation-of-cohesin-loading-factor-nipped-b-like-protein-nipbl-induces-cell-cycle-arrest-apoptosis-and-autophagy-of-breast-cancer-cell-lines
#15
Huanhuan Zhou, Lei Zheng, Kongbeng Lu, Yun Gao, Liwei Guo, Weizhen Xu, Xiaojia Wang
BACKGROUND The cohesin loading factor, nipped-B-like protein (NIPBL), is also known as the sister chromatid cohesion 2 (SCC2) human homolog. Recently, we have studied the role of expression levels of NIPBL in cell proliferation and chemotherapy resistance of non-small cell lung cancer (NSCLC) cells in vitro. The aim of this study was to investigate the effects of expression of the cohesin loading factor, NIPBL, on the cell cycle, apoptosis, and autophagy of breast cancer cell lines in vitro. MATERIAL AND METHODS Expression levels of the NIPBL in the breast cancer cell lines, MCF7, Bcap37, MDA-MB 453 and MDA-MB 231, were measured using Western blot and flow cytometry...
October 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28986166/sildenafil-induces-browning-of-subcutaneous-white-adipose-tissue-in-overweight-adults
#16
Shuguang Li, Yixiang Li, Lin Xiang, Jing Dong, Min Liu, Guangda Xiang
OBJECTIVE: To investigate that short-term treatment of sildenafil can induce browning of subcutaneous white adipose tissue (sWAT) in human adults. DESIGN: A randomized, double-blinded, placebo-controlled, parallel group trial. METHODS: Sixteen eligibility overweight male subjects were recruited, comparing 100 mg/day sildenafil versus an identical placebo therapy for 7 days. sWAT samples were collected from subjects before and after 7-day sildenafil or placebo intervention...
October 3, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28981117/trehalose-ameliorates-oxidative-stress-mediated-mitochondrial-dysfunction-and-er-stress-via-selective-autophagy-stimulation-and-autophagic-flux-restoration-in-osteoarthritis-development
#17
Qian Tang, Gang Zheng, Zhenhua Feng, Yu Chen, Yiting Lou, Chenggui Wang, Xiaolei Zhang, Yu Zhang, Huazi Xu, Ping Shang, Haixiao Liu
Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, we explored the potential protective effects of trehalose, a novel Mammalian Target of Rapamycin (mTOR)-independent autophagic inducer, in TBHP-treated mouse chondrocytes and a destabilized medial meniscus (DMM) mouse OA model...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28979680/low-concentration-of-chloroquine-enhanced-efficacy-of-cisplatin-in-the-treatment-of-human-ovarian-cancer-dependent-on-autophagy
#18
Jie Zhu, Ya Zheng, Haiyan Zhang, Jing Zhu, Hong Sun
BACKGROUND: Cisplatin is a common used anti-tumor drug in ovarian cancer therapy with potent effect. Studies have reported that autophagy works as a cell-survival process in cancer, chloroquine has been added to various chemotherapeutic drugs. In the current study, we aim to evaluate whether chloroquine can enhance the effects of cisplatin in treating ovarian cancer. METHODS: CCK-8 assay was used to detect cell viability. Transwell assay was used to examine cell migration and invasion...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28979133/targeted-inhibition-of-the-phosphoinositide-3-kinase-impairs-cell-proliferation-survival-and-invasion-in-colon-cancer
#19
Fei Yang, Jun-Yi Gao, Hua Chen, Zhen-Hua Du, Xue-Qun Zhang, Wei Gao
BACKGROUND: Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. METHODS: In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28978645/quantitative-phosphoproteomics-reveals-involvement-of-multiple-signaling-pathways-in-early-phagocytosis-by-the-retinal-pigmented-epithelium
#20
Cheng-Kang Chiang, Aleksander Tworak, Brian M Kevany, Bo Xu, Janice Mayne, Zhibin Ning, Daniel Figeys, Krzysztof Palczewski
One of the major biological functions of the retinal pigmented epithelium (RPE) is the clearance of shed photoreceptor outer segments (POS) through a multistep process resembling phagocytosis. RPE phagocytosis helps maintain the viability of photoreceptors that otherwise could succumb to the high metabolic flux and photo-oxidative stress associated with visual processing. The regulatory mechanisms underlying phagocytosis in the RPE are not fully understood, although dysfunction of this process contributes to the pathogenesis of multiple human retinal degenerative disorders, including age-related macular degeneration...
October 4, 2017: Journal of Biological Chemistry
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