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pi3k akt

Balal Brazvan, Abbas Ebrahimi-Kalan, Kobra Velaei, Ahmad Mehdipour, Zeynab Aliyari Serej, Ayyub Ebrahimi, Mohammad Ghorbani, Omid Cheraghi, Hojjatollah Nozad Charoudeh
The end of linear chromosomes is formed of a special nucleoprotein heterochromatin structure with repetitive TTAGGG sequences called telomere. Telomere length is regulated by a special enzyme called telomerase, a specific DNA polymerase that adds new telomeric sequences to the chromosome ends. Telomerase consists of two parts; the central protein part and the accessory part which is a RNA component transported by the central part. Regulation of telomere length by this enzyme is a multi-stage process. Telomere length elongation is strongly influenced by the level of telomerase and has a strong correlation with the activity of telomerase enzyme...
March 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
Md Moniruzzaman, Young-Won Chin, Jungsook Cho
Physalis alkekengi var. francheti is an indigenous herb well known for its anti-inflammatory, sedative, antipyretic, and expectorant properties. However, the information regarding the impacts of P. alkekengi fruits (PAF) in modulation of oxidative stress and learning memory are still unknown. This study therefore evaluated the antioxidant properties of ethyl acetate (EA) fraction of PAF and its impacts on learning and memory. The antioxidant activities of PAF were evaluated in LPS-induced BV2 microglial cells...
March 15, 2018: Cell Stress & Chaperones
Ji Wang, Chunying Wang, Gaofeng Bu
Cancer stem cells are considered as a main cause of cancer recurrence. In the present study, the effects of curcumin on the growth of liver cancer stem cells (LCSCs) were investigated. The proliferation and apoptosis of LCSCs were assessed by MTT assays and flow cytometry. Changes in the expression of apoptosis-related proteins were identified by western blotting. The results of the study demonstrated that curcumin treatment inhibited the growth of LCSCs, induced cell apoptosis, as well as regulated the expression of apoptosis-associated proteins and the release of cytochrome c...
April 2018: Experimental and Therapeutic Medicine
Chengzhi Fang, Lili Xie, Chunmei Liu, Chunhua Fu, Wei Ye, Hong Liu, Binghong Zhang
Neonatal necrotizing enterocolitis (NEC) is a severe acquired disease that predominantly affects the small intestine of neonates. NEC is caused by a combination of metabolic products, dysfunctions of the blood vessels, mucus and other unknown factors. Berberine may induce beneficial effects on necrotic and cardiovascular diseases due to its anti-inflammatory and anti-apoptotic effects on epithelial cells. In the present study, the therapeutic effects of berberine were investigated and the potential mechanisms by which it functions within a neonatal NEC mouse model were analyzed...
April 2018: Experimental and Therapeutic Medicine
Qianqian Wang, Jiahui Xu, Ying Li, Jumin Huang, Zebo Jiang, Yuwei Wang, Liang Liu, Elaine Lai Han Leung, Xiaojun Yao
Protein arginine methyltransferase 5 (PRMT5) is able to regulate gene transcription by catalyzing the symmetrical dimethylation of arginine residue of histone, which plays a key role in tumorigenesis. Many efforts have been taken in discovering small-molecular inhibitors against PRMT5, but very few were reported and most of them were SAM-competitive. EPZ015666 is a recently reported PRMT5 inhibitor with a new binding site, which is different from S-adenosylmethionine (SAM)-binding pocket. This new binding site provides a new clue for the design and discovery of potent and specific PRMT5 inhibitors...
2018: Frontiers in Pharmacology
He Wang, Jianjia Li, Xiaoyi Zhang, Tingting Ning, Dandan Ma, Yihong Ge, Shuaimei Xu, Yilin Hao, Buling Wu
To seek a potential target for periodontal tissue regeneration, this study aimed to explore the role of Integrin alpha 5 (ITGA5) in human periodontal ligament stem cells (PDLSCs). Transwell assay, Cell Counting Kit 8 (CCK8) assay, cell cycle assay, alkaline phosphatase (ALP) activity, alizarin red staining, and western blot were used to investigate the effects of ITGA5 on PDLSC migration, proliferation and osteogenic differentiation. The in vivo effect was investigated by nude mice subcutaneous transplantation with cell and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) complex...
March 12, 2018: Journal of Proteomics
Jing-Rong Kong, Wei Wei, Xue-Li Qiao, Huan Kang, Di Huang, Yuan Liu, Wei-Na Wang
It is well known that PI3K regulates various processes in mammalian cells by generating a secondary messenger that later activates AKT. However, its innate immune function in crustaceans remains unclear. We report the characterization of Litopenaeus vannamei PI3K (LvPI3K) for investigating how PI3K participates in the innate immunity of crustaceans. Full-length LvPI3K cDNA was 3357 bp long, with a 3222 bp open reading frame (ORF) that encodes a putative protein of 1292 amino acids. The PI3K catalytic domain (PI3Kc) of LvPI3K was found to be rather conserved when the PI3Ks from other species were analyzed...
March 12, 2018: Fish & Shellfish Immunology
Jared M Dickinson, Andrew C D'Lugos, Marcus A Naymik, Ashley L Siniard, Amanda J Wolfe, Donald P Curtis, Matthew J Huentelman, Chad C Carroll
Aerobic (AE) and resistance exercise (RE) elicit unique adaptations in skeletal muscle that have distinct implications for health and performance. The purpose of this study was to identify the unique transcriptome response of skeletal muscle to acute AE and RE. In a counter-balanced, cross-over design, six healthy, recreationally active young men (27{plus minus}3y) completed acute AE (40 min cycling, ~70% maximal HR) and RE (8 sets, 10 reps, ~65% 1RM), separated by ~1wk. Muscle biopsies ( vastus lateralis) were obtained before and at 1 and 4h post exercise...
March 15, 2018: Journal of Applied Physiology
Wen Zhang, Jun-Ke Song, Rong Yan, Li Li, Zhi-Yong Xiao, Wen-Xia Zhou, Zhen-Zhong Wang, Wei Xiao, Guan-Hua Du
Diterpene ginkgolides meglumine injection (DGMI) is a therapeutic extract of Ginkgo biloba L, which has been used for the treatment of cerebral ischemic stroke in China. Ginkgolides A, B and C are the main components of DGMI. This study was designed to investigate the neuroprotective effects of DGMI components against ischemic stroke in vivo and in vitro. Acute cerebral ischemic injury was induced in rats by occlusion of the middle cerebral artery (MCA) for 1.5 h followed by 24 h reperfusion. The rats were treated with DGMI (1, 3 and 10 mg/kg, iv) at the onset of reperfusion and 12 h after reperfusion...
March 15, 2018: Acta Pharmacologica Sinica
Tao Yu, Ning Li, Chengde Wu, Amy Guan, Yi Li, Zhengang Peng, Miao He, Jie Li, Zhen Gong, Lei Huang, Bo Gao, Dongling Hao, Jikui Sun, Yan Pan, Liang Shen, Chichung Chan, Xiulian Lu, Hongyu Yuan, Yongguo Li, Jian Li, Shuhui Chen
The identification and lead optimization of a series of pyridopyrimidinone derivatives are described as a novel class of efficacious dual PI3K/mTOR inhibitors, resulting in the discovery of 31 . Compound 31 exhibited high enzyme activity against PI3K and mTOR, potent suppression of Akt and p70s6k phosphorylation in cell assays, and good pharmacokinetic profile. Furthermore, compound 31 demonstrated in vivo efficacy in a PC-3M tumor xenograft model.
March 8, 2018: ACS Medicinal Chemistry Letters
Chengzheng Han, Guozheng Xing, Mengying Zhang, Min Zhong, Zhen Han, Chiyi He, Xiaoping Liu
Wogonoside, the main effective constituent of traditional Chinese medicine Scutellaria , belongs to the glucuronide family, with various functions, including detoxification, anti-inflammation and nourishing gallbladder, lowering blood pressure, diuresis and anti-allergic reactions. However, the effects of wogonoside on human colon cancer cells remain unclear. The present study aimed to investigate the anticancer effect of wogonoside on human colon cancer cells in vitro and its anticancer mechanisms. The results demonstrated that wogonoside significantly inhibited cell growth, induced apoptosis and mitochondrial-mediated autophagy of colon cancer cells...
April 2018: Oncology Letters
Conglin Ye, Xiaolong Yu, Xuqiang Liu, Min Dai, Bin Zhang
MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules involved in cancer initiation and progression. The present study aimed to determine the effect of miRNA-30d (miR-30d) on the growth, malignant phenotype, and apoptosis of Ewing's sarcoma (ES) SK-ES-1 cells, and to elucidate the underlying molecular mechanism and signaling pathway involved. Cell proliferation, invasion, migration, morphological changes, cell cycle distribution and apoptosis were investigated. Furthermore, the expression of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 and poly (ADP-ribose) polymerase (PARP) were examined, as was the activity of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt pathways...
April 2018: Oncology Letters
Shanshan Sun, Yansheng Wu, Wenyu Guo, Feng Yu, Lingping Kong, Yu Ren, Yu Wang, Xiaofeng Yao, Chao Jing, Chao Zhang, Mingyang Liu, Yuqing Zhang, Minghui Zhao, Zhaoqing Li, Chuanqiang Wu, Yu Qiao, Jingxuan Yang, Xudong Wang, Lun Zhang, Min Li, Xuan Zhou
PURPOSE: Phosphotidylinositol-3-kinase (PI3K)and signal transducers and activators of transcription 3 (STAT3) are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate HNSCC growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of head and neck squamous cell cancer (HNSCC). In this study, we attempted to establish the correlation of PI3K-STAT3-HOTAIR signaling with the progression of HNSCC and its sensitivity towards platinum-based and targeted anti-EGFR combination therapy...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Christina M McGuire, Michael Forgac
The vacuolar H+ -ATPase (V-ATPase) is an ATP-driven proton pump involved in many cellular processes. An important mechanism by which V-ATPase activity is controlled is the reversible assembly of its two domains, namely the peripheral V1 domain and the integral V0 domain. Although reversible assembly is conserved across all eukaryotic organisms, the signaling pathways controlling it have not been fully characterized. Here we identify glucose starvation as a novel regulator of V-ATPase assembly in mammalian cells...
March 14, 2018: Journal of Biological Chemistry
Nathália Kersting, Bárbara Kunzler Souza, Igor Araujo Vieira, Rafael Pereira Dos Santos, Danielly Brufatto Olguins, Lauro José Gregianin, André Tesainer Brunetto, Algemir Lunardi Brunetto, Rafael Roesler, Caroline Brunetto de Farias, Gilberto Schwartsmann
OBJECTIVE: Ewing sarcoma (ES) is a type of childhood cancer probably arising from stem mesenchymal or neural crest cells. The epidermal growth factor receptor (EGFR) acts as a driver oncogene in many types of solid tumors. However, its involvement in ES remains poorly understood. METHODS: Human SK-ES-1 and RD-ES ES cells were treated with EGF, the EGFR inhibitor tyrphostin (AG1478), or phosphoinositide 3-kinase (PI3K) or extracellular-regulated kinase (ERK)/mitogen-activated kinase (MAPK) inhibitors...
March 14, 2018: Oncology
Laura Rosenberg, Charles H Yoon, Gaurav Sharma, Monica M Bertagnolli, Nancy L Cho
Desmoid tumors (DTs) are unusual neoplasms of mesenchymal origin that exhibit locally invasive behavior. Surgical resection is the initial treatment of choice for DTs. For patients with recurrent or unresectable disease, however, medical options are limited. Sorafenib is a multikinase inhibitor with known anti-tumor activity in various cancers via suppression of the PI3K/Akt/mTOR pathway. Here, we examined the effects of sorafenib on patient-derived DT cell lines, with the aim of characterizing the efficacy and molecular mechanism of action...
March 10, 2018: Carcinogenesis
Cheng Zeng, Wen Jiang, Ruifang Zheng, Chenghui He, Jianguang Li, Jianguo Xing
Our previous research demonstrated that tilianin protects the myocardium in a myocardial ischemia reperfusion injury (MIRI) rat model and has prominent pharmacological potential as a cardiovascular drug. Our study aimed to investigate the molecular signaling implicated in the improvement of myocardial survival induced by tilianin, a flavonoid antioxidant. Tilianin (2.5, 5, and 10 mg/kg/d) or saline was orally administered to rats for 14 days. On the 15th day, ischemia was induced by ligating the left anterior descending artery for 45 min, followed by 4 h of reperfusion...
2018: PloS One
Jiangyong Gu, Li Li, Dongmei Wang, Wei Zhu, Ling Han, Ruizhi Zhao, Xiaojie Xu, Chuanjian Lu
Psoriasis vulgaris is a chronic inflammatory and immune-mediated skin disease. 44 metabonomics biomarkers were identified by high-throughput liquid chromatography coupled to mass spectrometry in our previous work. To further explore the roles of metabonomics biomarkers in the pathogenesis of psoriasis, the metabonomics biomarker-enzyme network was constructed. The key metabonomics biomarkers and enzymes were screened out by network analysis. Long-chain fatty acids, phospholipids, Estradiol and NADH were the most important metabonomics biomarkers...
March 14, 2018: Annals of Medicine
Kumar Parijat Tripathi, Marina Piccirillo, Mario Rosario Guarracino
BACKGROUND: The endomembrane system, known as secretory pathway, is responsible for the synthesis and transport of protein molecules in cells. Therefore, genes involved in the secretory pathway are essential for the cellular development and function. Recent scientific investigations show that ER and Golgi apparatus may provide a convenient drug target for cancer therapy. On the other hand, it is known that abundantly expressed genes in different cellular organelles share interconnected pathways and co-regulate each other activities...
March 8, 2018: BMC Bioinformatics
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