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https://www.readbyqxmd.com/read/28422956/chronic-activation-of-ppar%C3%AE-with-fenofibrate-reduces-autophagic-proteins-in-the-liver-of-mice-independent-of-fgf21
#1
Eunjung Jo, Songpei Li, Qingning Liang, Xinmei Zhang, Hao Wang, Terence P Herbert, Trisha A Jenkins, Aimin Xu, Ji-Ming Ye
Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARα may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARα with fenofibrate (FB) in mice. Chronic administration of the PPARα agonist FB substantially reduced the levels of multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1) which were associated with a decrease in the light chain LC3II/LC3I ratio and the accumulation of p62...
2017: PloS One
https://www.readbyqxmd.com/read/28410220/reprogramming-induced-by-isoliquiritigenin-diminishes-melanoma-cachexia-through-mtorc2-akt-gsk3%C3%AE-signaling
#2
Xiao-Yu Chen, De-Fang Li, Ji-Chun Han, Bo Wang, Zheng-Ping Dong, Li-Na Yu, Zhao-Hai Pan, Chuan-Jun Qu, Ying Chen, Shi-Guo Sun, Qiu-Sheng Zheng
Isoliquiritigenin (ISL), a member of the flavonoids, is known to have anti-tumor activity in vitro and in vivo. The effect of ISL on reprogramming in cancer cells, however, remains elusive. In this study, we investigated the effect of ISL on reprogramming in human melanoma A375 cells. ISL (15 μg/ml) significantly inhibited A375 cell proliferation, anchorage independent cell proliferation and G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no significant changes in apoptosis rate. Terminal differentiation indicators (melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were all up-regulated by ISL treatment...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396841/ubiquitin-ligase-smurf1-functions-as-a-prognostic-marker-and-promotes-growth-and-metastasis-of-clear-cell-renal-cell-carcinoma
#3
Mang Ke, Licai Mo, Weilin Li, Xianjun Zhang, Feiping Li, Hongyuan Yu
Smad ubiquitin regulatory factor 1 (SMURF1), a recently identified E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation. Previous studies have reported that SMURF1 also functions as an oncogene in human cancers. However, the clinical value of SMURF1 and its role in clear cell renal cell carcinoma (ccRCC) are unknown. SMURF1 expression was analyzed in 100 cases of ccRCC and matched tumor-adjacent specimens. SMURF1 was prominently overexpressed in ccRCC specimens compared with tumor-adjacent specimens...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28396363/genomic-and-molecular-screenings-identify-different-mechanisms-for-acquired-resistance-to-met-inhibitors-in-lung-cancer-cells
#4
Pol Gimenez-Xavier, Eva Pros, Ester Bonastre, Sebastian Moran, Ana Aza, Osvaldo Graña, Gonzalo Gómez-López, Sophia Derdak, Marc Dabad, Anna Esteve-Codina, Jose R Hernandez Mora, Diana Salinas-Chaparro, Manel Esteller, David Pisano, Montse Sanchez-Cespedes
The development of resistance to tyrosine kinase inhibitors (TKIs) limits the long-term efficacy of cancer treatments involving them. We aimed to understand the mechanisms that underlie acquired resistance (AR) to MET inhibitors in lung cancer. EBC1 cells, which have MET amplification and are sensitive to TKIs against MET, were used to generate multiple clones with AR to a MET-TKI. Whole-exome sequencing, RNA sequencing and global DNA methylation analysis were used to scrutinize the genetic and molecular characteristics of the resistant cells...
April 10, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28392705/long-noncoding-rna-linc01296-is-associated-with-poor-prognosis-in-prostate-cancer-and-promotes-cancer-cell-proliferation-and-metastasis
#5
Jie Wu, Gong Cheng, Cheng Zhang, Yuxiao Zheng, Haoxiang Xu, Haiwei Yang, Lixin Hua
BACKGROUND/PURPOSE: Long noncoding RNAs (lncRNAs) have emerged as important regulators and biomarkers of tumor development and progression. This study investigated the clinical significance, biological functions, and underlying mechanisms of long intergenic non-protein-coding RNA 1296 (LINC01296) in prostate cancer. MATERIALS AND METHODS: LINC01296 expression in prostate cancer tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28387249/lanatoside-c-a-cardiac-glycoside-acts-through-protein-kinase-c%C3%AE-to-cause-apoptosis-of-human-hepatocellular-carcinoma-cells
#6
Min-Wu Chao, Tzu-Hsuan Chen, Han-Li Huang, Yu-Wei Chang, Wei-Chun HuangFu, Yu-Ching Lee, Che-Ming Teng, Shiow-Lin Pan
Recent studies have revealed that cardiac glycosides, such as digitalis and digoxin, have anticancer activity and may serve as lead compounds for the development of cancer treatments. The poor prognosis of hepatocellular carcinoma (HCC) patients reflects the development of resistance to current chemotherapeutic agents, highlighting the need for discovering new small-molecule therapeutics. Here, we found that lanatoside C, an anti-arrhythmic agent extracted from Digitalis lanata, inhibited the growth of HCC cells and dramatically decreased tumor volume as well as delayed tumor growth without obvious body weight loss...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28382169/integration-of-receptor-tyrosine-kinases-determines-sensitivity-to-pi3k%C3%AE-selective-inhibitors-in-breast-cancer
#7
Yi-Chao Xu, Xiang Wang, Yi Chen, Si-Meng Chen, Xin-Ying Yang, Yi-Ming Sun, Mei-Yu Geng, Jian Ding, Ling-Hua Meng
PI3Kα-selective inhibitor BYL719 is currently in phase II/III clinical trial for the treatment of breast cancer, but highly variable response has been observed among patients. We sought to discover predictive biomarker for the efficacy of BYL719 by dissecting the proliferative signaling pathway mediated by PI3K in breast cancer. BYL719 concurrently inhibited the phosphorylation of AKT and ERK in PIK3CA-mutated human breast cancer cells. PI3K-regulated ERK phosphorylation was independent of canonical PDK1/AKT/mTOR pathway, while it was associated with RAF/MEK...
2017: Theranostics
https://www.readbyqxmd.com/read/28380429/ccl5-establishes-an-autocrine-high-grade-glioma-growth-regulatory-circuit-critical-for-mesenchymal-glioblastoma-survival
#8
Yuan Pan, Laura J Smithson, Yu Ma, Dolores Hambardzumyan, David H Gutmann
Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a median survival of 15 months. These poor clinical outcomes have prompted the development of drugs that block neoplastic cancer cell growth; however, non-neoplastic cell-derived signals (chemokines and cytokines) in the tumor microenvironment may also represent viable treatment targets. One such chemokine, Ccl5, produced by low-grade tumor-associated microglia, is responsible for maintaining neurofibromatosis type 1 (NF1) mouse optic glioma growth in vivo...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28288862/autophagy-inhibits-c2-ceramide-mediated-cell-death-by-decreasing-the-reactive-oxygen-species-levels-in-sh-sy5y-cells
#9
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
#10
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
#11
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
#12
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...
May 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
#13
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)...
May 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
#14
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
#15
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
#16
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...
May 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
#17
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
#18
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
#19
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
#20
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
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