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https://www.readbyqxmd.com/read/28288862/autophagy-inhibits-c2-ceramide-mediated-cell-death-by-decreasing-the-reactive-oxygen-species-levels-in-sh-sy5y-cells
#1
Chenghe Fan, Yuanyuan Liu, Mingming Zhao, Rui Zhan, Wei Cui, Haiqiang Jin, Yuming Teng, Pu Lv, Lemin Zheng, Yining Huang
Ceramide has been recognized as a second messenger that regulates several intracellular processes in neuronal cells. However, its role in neuronal autophagy is not fully understood. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to investigate the mechanisms underlying C2-ceramide-mediated cell death and autophagy. C2-ceramide induced caspase-3-independent cell death. In addition, C2-ceramide induced autophagy, decreased the activation of Akt and mTOR, and increased the activation of JNK and ERK1/2...
March 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28274614/metformin-represses-glucose-starvation-induced-autophagic-response-in-microvascular-endothelial-cells-and-promotes-cell-death
#2
Samson Mathews Samuel, Suparna Ghosh, Yasser Majeed, Gnanapragasam Arunachalam, Mohamed M Emara, Hong Ding, Chris R Triggle
Metformin, the most frequently administered drug for the treatment of type 2 diabetes, is being investigated for its potential in the treatment of various types of cancer; however, the cellular basis for this putative anti-cancer action remains controversial. In the current study we examined the effect of metformin on endoplasmic reticulum (ER) stress and autophagy in glucose-starved micro-vascular endothelial cells (MECs). The rationale for our experimental protocol is that in a growing tumor MECs are subjected to hypoxia and nutrient/glucose starvation that results from the reduced supply and relatively high consumption of glucose...
March 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28272775/cryptotanshinone-inhibition-of-mammalian-target-of-rapamycin-pathway-is-dependent-on-oestrogen-receptor-alpha-in-breast-cancer
#3
Yanhong Pan, Junfeng Shi, Wenting Ni, Yuping Liu, Siliang Wang, Xu Wang, Zhonghong Wei, Aiyun Wang, Wenxing Chen, Yin Lu
Cryptotanshinone (CPT) has been demonstrated to inhibit proliferation and mammalian target of rapamycin (mTOR) pathway in MCF-7 breast cancer cells. However, the same results are unable to be repeated in MDA-MB-231 cells. Given the main difference of oestrogen receptor α (ERα) between two types of breast cancer cells, It is possibly suggested that CPT inhibits mTOR pathway dependent on ERα in breast cancer. CPT could significantly inhibit cell proliferation of ERα-positive cancer cells, whereas ERα-negative cancer cells are insensitive to CPT...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28237591/methionine-leucine-isoleucine-or-threonine-effects-on-mammary-cell-signaling-and-pup-growth-in-lactating-mice
#4
G M Liu, M D Hanigan, X Y Lin, K Zhao, F G Jiang, R R White, Y Wang, Z Y Hu, Z H Wang
Two studies were undertaken to assess the effects of individual essential AA supplementation of a protein-deficient diet on lactational performance in mice using litter growth rates as a response variable. The first study was designed to establish a dietary protein response curve, and the second to determine the effects of Leu, Ile, Met, and Thr supplementation of a protein-deficient diet on lactational performance. In both studies, dams were fed test diets from parturition through d 17 of lactation, when the studies ended...
February 22, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28237515/adiporon-an-adiponectin-receptor-agonist-attenuates-pdgf-induced-vsmc-proliferation-through-inhibition-of-mtor-signaling-independent-of-ampk-implications-toward-suppression-of-neointimal-hyperplasia
#5
Arwa Fairaq, Noha M Shawky, Islam Osman, Prahalathan Pichavaram, Lakshman Segar
Hypoadiponectinemia is associated with an increased risk of coronary artery disease. Although adiponectin replenishment mitigates neointimal hyperplasia and atherosclerosis in mouse models, adiponectin therapy has been hampered in a clinical setting due to its large molecular size. Recent studies demonstrate that AdipoRon (a small-molecule adiponectin receptor agonist) improves glycemic control in type 2 diabetic mice and attenuates postischemic cardiac injury in adiponectin-deficient mice, in part, through activation of AMP-activated protein kinase (AMPK)...
February 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28230926/association-between-high-expression-of-phosphorylated-akt-and-mammalian-target-of-rapamycin-and-improved-survival-in-salivary-gland-adenoid-cystic-carcinoma
#6
Dai-Qiao Ouyang, Li-Zhong Liang, Zun-Fu Ke, Guang-Sen Zheng, De-Sheng Weng, Wei-Fa Yang, Yu-Xiong Su, Gui-Qing Liao
BACKGROUND: Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported. METHODS: P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rβ) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data...
February 23, 2017: Head & Neck
https://www.readbyqxmd.com/read/28223119/neferine-augments-therapeutic-efficacy-of-cisplatin-through-ros-mediated-non-canonical-autophagy-in-human-lung-adenocarcinoma-a549%C3%A2-cells
#7
Sivalingam Kalai Selvi, Amirthalingam Vinoth, Thiyagarajan Varadharajan, Ching Feng Weng, Viswanadha Vijaya Padma
Combination of dietary components with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Neferine, major bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (Lotus). In the present study, we investigated the efficacy of the combinatorial regimen of neferine and cisplatin compared to cisplatin high dose in human lung adenocarcinoma (A549) cells. Co-treatment with neferine enhanced cisplatin-induced autophagy in A549 cells was accompanied by Acidic vesicular accumulation (AVO), enhanced generation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH), down regulation of PI3K/AKT/mTOR pathway, conversion of LC3B-I to LC3B-II...
February 20, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28212891/sulforaphane-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cell-proliferation-by-targeting-mtor-p70s6kinase-signaling-independent-of-nrf2-activation
#8
Noha M Shawky, Lakshman Segar
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28193689/signaling-by-fgf-receptor-2-not-fgf-receptor-1-regulates-myelin-thickness-through-activation-of-erk1-2-mapk-which-promotes-mtorc1-activity-in-an-akt-independent-manner
#9
Miki Furusho, Akihiro Ishii, Rashmi Bansal
FGF signaling has emerged as a significant "late-stage" regulator of myelin thickness in the CNS, independent of oligodendrocyte differentiation. Therefore, it is critically important to identify the specific FGF receptor type and its downstream signaling molecules in oligodendrocytes to obtain better insights into the regulatory mechanisms of myelin growth. Here, we show that FGF receptor type 2 (FGFR2) is highly enriched at the paranodal loops of myelin. Conditional ablation of this receptor-type, but not FGF receptor type 1 (FGFR1), resulted in attenuation of myelin growth, expression of major myelin genes, key transcription factor Myrf and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) activity...
March 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28192480/mtor-activity-in-aids-related-diffuse-large-b-cell-lymphoma
#10
Sara H Browne, Julio A Diaz-Perez, Michael Preziosi, Charles C King, George A Jones, Sonia Jain, Xiaoying Sun, Erin G Reid, Scott VandenBerg, Huan-You Wang
BACKGROUND: Patients infected with HIV have a significantly increased risk of developing non-Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS) related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K), an extensively studied effector of mTOR Complex 1 (mTORC1) and the phosphorylated phosphatase and tensin homolog (pPTEN), a negative regulator of mTORC1 pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28159918/protein-drug-target-activation-homogeneity-in-the-face-of-intra-tumor-heterogeneity-implications-for-precision-medicine
#11
Erika Maria Parasido, Alessandra Silvestri, Vincenzo Canzonieri, Claudio Belluco, Maria Grazia Diodoro, Massimo Milione, Flavia Melotti, Ruggero De Maria, Lance Liotta, Emanuel F Petricoin, Mariaelena Pierobon
INTRODUCTION: Recent studies indicated tumors may be comprised of heterogeneous molecular subtypes and incongruent molecular portraits may emerge if different areas of the tumor are sampled. This study explored the impact of intra-tumoral heterogeneity in terms of activation/phosphorylation of FDA approved drug targets and downstream kinase substrates. MATERIAL AND METHODS: Two independent sets of liver metastases from colorectal cancer were used to evaluate protein kinase-driven signaling networks within different areas using laser capture microdissection and reverse phase protein array...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/28158902/metformin-attenuates-albumin-induced-alterations-in-renal-tubular-cells-in-vitro
#12
Soumaya Allouch, Shankar Munusamy
Proteinuria (albuminuria) plays a crucial role in the etiology of chronic kidney disease (CKD) via alteration of multiple signaling pathways and cellular process in renal cells. The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury...
February 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28153093/human-amniocytes-are-receptive-to-chemically-induced-reprogramming-to-pluripotency
#13
Kate E Hawkins, Dafni Moschidou, Danilo Faccenda, Wasco Wruck, Alex Martin-Trujillo, Kwan-Leong Hau, Anna Maria Ranzoni, Veronica Sanchez-Freire, Fabio Tommasini, Simon Eaton, Paolo De Coppi, David Monk, Michelangelo Campanella, Adrian J Thrasher, James Adjaye, Pascale V Guillot
Restoring pluripotency using chemical compounds alone would be a major step forward in developing clinical-grade pluripotent stem cells, but this has not yet been reported in human cells. We previously demonstrated that VPA_AFS cells, human amniocytes cultivated with valproic acid (VPA) acquired functional pluripotency while remaining distinct from human embryonic stem cells (hESCs), questioning the relationship between the modulation of cell fate and molecular regulation of the pluripotency network. Here, we used single-cell analysis and functional assays to reveal that VPA treatment resulted in a homogeneous population of self-renewing non-transformed cells that fulfill the hallmarks of pluripotency, i...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28152510/akt-mtor-mediated-induction-of-bystander-effect-signaling-in-a-nucleus-independent-manner-in-irradiated-human-lung-adenocarcinoma-epithelial-cells
#14
Lu Li, Lu Wang, Kevin M Prise, K N Yu, Guodong Chen, Lianyun Chen, Yide Mei, Wei Han
Cytoplasm is an important target for the radiation-induced bystander effect (RIBE). In the present work, the critical role of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in the generation of RIBE signaling after X-ray irradiation and the rapid phosphorylation of Akt and mTOR was observed in the cytoplasm of irradiated human lung adenocarcinoma epithelial (A549) cells. Targeting A549 cytoplasts with individual protons from a microbeam showed that RIBE signal(s) mediated by the Akt/mTOR pathway were generated even in the absence of a cell nucleus...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143890/localization-of-mtorc2-activity-inside-cells
#15
Michael Ebner, Benjamin Sinkovics, Magdalena Szczygieł, Daniela Wolfschoon Ribeiro, Ivan Yudushkin
Activation of protein kinase Akt via its direct phosphorylation by mammalian target of rapamycin (mTOR) complex 2 (mTORC2) couples extracellular growth and survival cues with pathways controlling cell growth and proliferation, yet how growth factors target the activity of mTORC2 toward Akt is unknown. In this study, we examine the localization of the obligate mTORC2 component, mSin1, inside cells and report the development of a reporter to examine intracellular localization and regulation by growth factors of the endogenous mTORC2 activity...
February 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28141785/anti-tumor-effects-of-atractylenolide-i-on-human-ovarian-cancer-cells
#16
Fangyi Long, Ting Wang, Ping Jia, Huafei Wang, Yi Qing, Tingting Xiong, Mengjie He, Xiaoli Wang
BACKGROUND The aim of this study was to investigate the effects of Atractylenolide-I (AT-I), a naturally occurring sesquiterpene lactone isolated from Atractylodes macrocephala Koidz, on human ovarian cancer cells. MATERIAL AND METHODS The viability and anchorage-independent growth of ovarian cancer cells were evaluated using MTT and colony formation assay, respectively. Cell cycle and apoptosis were detected with flow cytometry analysis. The level of cyclin B1 and CDK1 was measured using qPCR and ELISA analysis...
January 31, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28132115/rictor-expression-in-esophageal-squamous-cell-carcinoma-and-its-clinical-significance
#17
Wei-Jia Jiang, Ru-Xue Feng, Jia-Tao Liu, Lu-Lu Fan, Hua Wang, Guo-Ping Sun
Esophageal cancer is one of the most common malignant tumors in the world, and its incidence is the eighth highest; meanwhile, its fatality rate is the sixth highest. The PI3K/Akt/mTOR signaling pathway plays a required role in human cancer, including cell survival, metabolism and migration. As a kind of important scaffold protein in mTORC2, RICTOR has showed over-expression in several malignancies like melanoma and endometrial cancer. In this research, we selected 201 cases of paraffin specimens from patients diagnosed as esophageal squamous cell carcinoma after surgical treatment and then estimated the RICTOR expression in each esophageal squamous cell carcinoma tissue by using the immunohistochemical streptavidin-peroxidase technique...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28123607/proteins-involved-in-her2-signalling-pathway-their-relations-and-influence-on-metastasis-free-survival-in-her2-positive-breast-cancer-patients-treated-with-trastuzumab-in-adjuvant-setting
#18
Agnieszka Adamczyk, Aleksandra Grela-Wojewoda, Małgorzata Domagała-Haduch, Aleksandra Ambicka, Agnieszka Harazin-Lechowska, Anna Janecka, Ida Cedrych, Kaja Majchrzyk, Anna Kruczak, Janusz Ryś, Joanna Niemiec
AIM: Resistance to trastuzumab (which is a standard therapy for breast cancer patients with HER2 overexpression) is associated with higher risk of progression or cancer death, and might be related to activation of signalling cascades (PI3K/AKT/mTOR, Ras/Raf/MAPK) and decreased level of their inhibitors. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28108221/sirtuin-1-independent-effects-of-resveratrol-in-ins-1e-%C3%AE-cells
#19
Cihan S Erdogan, Mathias Mørup-Lendal, Louise T Dalgaard, Ole Vang
Resveratrol (Resv), a natural polyphenol, is suggested to have various health benefits including improved insulin sensitivity. Resv activates Sirtuin (Sirt1) in several species and tissues. Sirt1 is a protein deacetylase with an important role in ageing, metabolism and β-cell function. In insulinoma β-cells (INS-1E), Resv is previously shown to improve glucose-stimulated insulin secretion in a Sirt1-dependent mechanism and to protect against β-cell dedifferentiation in non-human primates, while inducing hypertrophy in myoblasts...
February 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28104681/copy-number-variations-of-e2f1-a-new-genetic-risk-factor-for-testicular-cancer
#20
Maria Santa Rocca, Andrea Di Nisio, Arianna Marchiori, Marco Ghezzi, Giuseppe Opocher, Carlo Foresta, Alberto Ferlin
Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy-number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer...
January 19, 2017: Endocrine-related Cancer
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