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https://www.readbyqxmd.com/read/28526951/pyrocincholic-acid-3%C3%AE-o-%C3%AE-d-quinovopyranosyl-28-o-%C3%AE-d-glucopyranoside-suppresses-adipogenesis-and-regulates-lipid-metabolism-in-3t3-l1-adipocytes
#1
Li Peng, Yanting Lu, Yuhui Xu, Jing Hu, Fang Wang, Yumei Zhang, Wenyong Xiong
Obesity is crucially involved in many metabolic diseases, such as type 2 diabetes, cardiovascular disease and cancer. Regulating the number or size of adipocytes has been suggested to be a potential treatment for obesity. In this study, we investigated the effect of pyrocincholic acid 3β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (PAQG), a 27-nor-oleanolic acid saponin extracted from Metadina trichotoma, on adipogenesis and lipid metabolism in 3T3-L1 adipocytes. The 3T3-L1 pre-adipocytes were incubated with vehicle or PAQG for 6 days in differentiation process...
May 19, 2017: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/28525387/sestrin-2-suppresses-cells-proliferation-through-ampk-mtorc1-pathway-activation-in-colorectal-cancer
#2
Jin-Lai Wei, Min Fang, Zhong-Xue Fu, Shou-Ru Zhang, Jin-Bao Guo, Rong Wang, Zhen-Bing Lv, Yong-Fu Xiong
Sestrin 2 is a conserved antioxidant protein that reduces reactive oxygen species (ROS) and inhibits mammalian target of rapamycin complex 1 (mTORC1). We previously showed that sestrin 2 is abnormally decreased in colorectal cancer (CRC). To elucidate the molecular mechanism behind the potential contribution of sestrin 2 to CRC, we used a lentiviral expression vector system to determine the effects of sestrin 2 overexpression on human CRC cells. We found that sestrin 2 overexpression decreased ROS production, inhibited cell growth, and stimulated apoptosis in two CRC cell lines...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522753/cyclin-d1-restrains-oncogene-induced-autophagy-by-regulating-the-ampk-lkb1-signaling-axis
#3
Mathew C Casimiro, Gabriele Di Sante, Agnese Di Rocco, Emanuele Loro, Claudia Pupo, Tim Pestell, Sara Bisetto, Marco A Velasco-Velàzquez, Xuanmao Jiao, Zhiping Li, Christine M Kusminski, Erin L Seifert, Chenguang Wang, Daniel Ly, Bin Zheng, Che-Hung Shen, Philipp E Scherer, Richard G Pestell
Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclinD1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that Cyclin D1 inhibited mitochondrial function, promoted glycolysis and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28518138/betulin-exhibits-anti-inflammatory-activity-in-lps-stimulated-macrophages-and-endotoxin-shocked-mice-through-an-ampk-akt-nrf2-dependent-mechanism
#4
Xinxin Ci, Junfeng Zhou, Hongming Lv, Qinlei Yu, Liping Peng, Shucheng Hua
Continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer. Nuclear factor erythroid 2-related factor (Nrf2), a critical transcriptional activator for antioxidative responses, has envolved to be an attractive drug target for the treatment or prevention of human diseases. In the present study, we investigated the effects and mechanisms of betulin on Nrf2 activation and its involvement in the lipopolysaccharide (LPS)-triggered inflammatory system...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28512260/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#5
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507102/foxo3-pgc-1%C3%AE-signaling-axis-is-essential-for-cancer-stem-cell-properties-of-pancreatic-ductal-adenocarcinoma
#6
Motofumi Kumazoe, Mika Takai, Shun Hiroi, Chieri Takeuchi, Mai Kadomatsu, Takashi Nojiri, Hiroaki Onda, Jaehoon Bae, Yuhui Huang, Kanako Takamatsu, Shuya Yamashita, Kenji Kangawa, Hirofumi Tachibana
In 95% of patients with pancreatic ductal adenocarcinoma (PDAC), recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anti-cancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knockin/knock down experiments and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)/PPAR-γ co-activator-1β (PGC- 1β)/pyruvate dehydrogenase -A1 (PDHA1) pathway is essential for CD44 expression and CSC properties...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28502587/direct-and-indirect-activation-of-eukaryotic-elongation-factor-2-kinase-by-amp-activated-protein-kinase
#7
M Johanns, S Pyr Dit Ruys, A Houddane, D Vertommen, G Herinckx, L Hue, C G Proud, M H Rider
BACKGROUND: Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a key regulator of protein synthesis in mammalian cells. It phosphorylates and inhibits eEF2, the translation factor necessary for peptide translocation during the elongation phase of protein synthesis. When cellular energy demand outweighs energy supply, AMP-activated protein kinase (AMPK) and eEF2K become activated, leading to eEF2 phosphorylation, which reduces the rate of protein synthesis, a process that consumes a large proportion of cellular energy under optimal conditions...
May 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28500773/the-energy-sensing-lkb1-ampk%C3%AE-1-pathway-regulates-igf1-secretion-and-consequent-activation-of-the-igf1r-pkb-pathway-in-primary-hepatocytes
#8
Liang Chen, Qiaoli Chen, Ping Rong, Hong Yu Wang, Shuai Chen
The insulin-like growth factor 1 (IGF1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well-established regulatory mechanisms controlling IGF1 expression, molecular mechanisms regulating of its secretion is not fully understood. The AMP-activated protein kinase (AMPK) is a key energy sensor, and accumulative evidence shows that AMPK is an attractive therapeutic target for treatment of diabetes, cancer and aging. Here we found that deficiency of AMPK promoted IGF1 secretion in mouse primary hepatocytes...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28498463/mir-138-suppresses-the-proliferation-metastasis-and-autophagy-of-non-small-cell-lung-cancer-by-targeting-sirt1
#9
Zaiting Ye, Bingmu Fang, Jiongwei Pan, Ning Zhang, Jinwei Huang, Congying Xie, Tianzheng Lou, Zhuo Cao
The present study determined the role and mechanism of miR-138 in non-small cell lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were collected. The expression of miR-138 in tissues and cell lines were determined by real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3 cells in vitro, and then the effects of miR-138 on lung cancer cell proliferation, cell cycle, invasion and metastasis were investigated by CCK-8 assay, Transwell and flow cytometry, respectively...
May 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28496098/combined-treatment-with-metformin-and-2-deoxy-glucose-induces-detachment-of-viable-mda-mb-231-breast-cancer-cells-in-vitro
#10
Maruša Bizjak, Petra Malavašič, Klemen Dolinar, Jelka Pohar, Sergej Pirkmajer, Mojca Pavlin
Triple naegative breast cancer has an increased rate of distant metastasis and consequently poor prognosis. To metastasize, breast cancer cells must detach from the main tumour mass and resist anoikis, a programmed cell death induced by lack of cell-extracellular matrix communication. Although cancer cells must detach to metastasize in vivo, the viability of floating cancer cells in vitro is rarely investigated. Here we show that co-treatment of anoikis-resistant MDA-MB-231 cells with metformin and 2-deoxy-D-glucose (2-DG) increased the percentage of floating cells, of which about 95% were viable...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28492544/halofuginone-dually-regulates-autophagic-flux-through-nutrient-sensing-pathways-in-colorectal-cancer
#11
Guo-Qing Chen, Rui-Hong Gong, Da-Jian Yang, Ge Zhang, Ai-Ping Lu, Siu-Cheong Yan, Shu-Hai Lin, Zhao-Xiang Bian
Autophagy has a key role in metabolism and impacts on tumorigenesis. Our previous study found that halofuginone (HF) exerts anticancer activity in colorectal cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. But whether and how HF regulates autophagy and metabolism to inhibit cancer growth remains an open question. Here, we unveil that HF activates ULK1 by downregulation of its phosphorylation site at Ser757 through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux under nutrient-rich condition...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28491867/metabolic-reprogramming-in-glioma
#12
REVIEW
Marie Strickland, Elizabeth A Stoll
Many cancers have long been thought to primarily metabolize glucose for energy production-a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28489607/trans-scirpusin-a-showed-antitumor-effects-via-autophagy-activation-and-apoptosis-induction-of-colorectal-cancer-cells
#13
Eun-Hye Hong, Eun-Young Heo, Jae-Hyoung Song, Bo-Eun Kwon, Jae-Young Lee, Yaejeong Park, Jinwoong Kim, Sun-Young Chang, Young-Won Chin, Sang-Min Jeon, Hyun-Jeong Ko
Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28475405/the-codon-72-polymorphism-of-p53-influences-cell-fate-following-nutrient-deprivation
#14
Che-Pei Kung, Qin Liu, Maureen E Murphy
The TP53 gene is distinguished as the most frequently mutated gene in cancer. Unlike most cancer-relevant genes, the TP53 gene is also distinguished by the existence of coding region polymorphisms that alter p53 sequence, and in some cases, also alter p53 function. A common coding region variant at amino acid 72 of p53 encodes either proline (P72) or arginine (R72). P72 is the ancestral variant and is most common in populations near the equator. The frequency of the R72 variant increases in a linear manner with latitude...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28469776/inhibition-of-ampk-related-kinase-5-ark5-enhances-cisplatin-cytotoxicity-in-non-small-cell-lung-cancer-cells-through-regulation-of-epithelial-mesenchymal-transition
#15
Minghui Li, Chengfei Zheng, Hongfei Xu, Wei He, Yongchun Ruan, Jianyong Ma, Junnan Zheng, Chengmeng Ye, Weidong Li
Lung cancer incidence and mortality rates are amongst the highest of all malignant tumors worldwide. ARK5 is a member of the human AMP-activated protein kinase (AMPK) family which is implicated in tumor survival and progression. The current study was designed to explore the role of ARK5 in resistance of non-small cell lung cancer (NSCLC) to cisplatin. We studied the sensitivity of two NSCLC cell lines, NCI-H1229 and A549, to cisplatin by using proliferation and cell viability assays. We then examined expression of ARK5, Twist, and the epithelial to mesenchymal transition (EMT) biomarkers, E-cadherin and Vimentin, by Western blot and immunofluorescence...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28467805/paraoxonase-1-pon1-induces-metastatic-potential-and-apoptosis-escape-via-its-antioxidative-function-in-lung-cancer-cells
#16
Mark Borris D Aldonza, Yeon Sung Son, Hye-Jin Sung, Jung-Mo Ahn, Young-Jin Choi, Yong-In Kim, Sukki Cho, Je-Yoel Cho
Paraoxonase-1 (PON1) gene polymorphisms have been closely associated with the development of advanced cancers while PON1 secretion to the serum is linked with inhibition of oxidized high-density lipoprotein by its antioxidative function. Our group previously demonstrated that post-translational modification of serum PON1 in form of fucosylated PON1 is a potential biomarker of small cell lung cancer. Here, we interrogated the role of PON1 in the pathobiology of lung cancer (LC) by addressing cell-autonomous mechanisms using gain-of-function and loss-of-function approaches and protein expression profiling of tissue samples in our clinical biobank...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28463901/a-mechanism-underlying-preventive-effect-of-high-intensity-training-on-colon-cancer
#17
Kaori Matsuo, Koji Sato, Ken Suemoto, Eri Miyamoto-Mikami, Noriyuki Fuku, Kazuhiko Higashida, Katsunori Tsuji, Yuzhong Xu, Xin Liu, Motoyuki Iemitsu, Takafumi Hamaoka, Izumi Tabata
INTRODUCTION: We examined effects of high intensity training on chemically induced aberrant crypt foci (ACF) in rat colon. We also investigated mechanisms that may underlie the results obtained, with a focus on secreted protein acidic and rich in cysteine (SPARC), which has been proposed as an exercise-related factor of colon cancer prevention. METHODS: After an administration of 1,2-dimethylhydrazine (DMH), F344 rats executed high-intensity intermittent swimming training (HIIST) (twelve 20-sec swimming with a weight [16% body weight] with 10-sec pauses between the bouts) 5 days/week for 4 weeks...
May 2, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28460359/synthesis-and-biological-evaluation-of-benzimidazole-derivatives-as-the-g9a-histone-methyltransferase-inhibitors-that-induce-autophagy-and-apoptosis-of-breast-cancer-cells
#18
Jin Zhang, Dahong Yao, Yingnan Jiang, Jian Huang, Shilin Yang, Jinhui Wang
G9a (also known as KMT1C or EHMT2) is initially identified as a H3K9 methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. It is overexpressed in various human cancers and employed as a promising target in cancer therapy. We discovered a benzoxazole scaffold through virtual high-throughput screening, and designed, synthesized 24 derivatives and investigated for inhibition of G9a. After several rounds of kinase and anti-proliferative activity screening, we discovered a potent G9a antagonist (GA001) with an IC50 value of 1...
April 17, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28453226/palbociclib-induces-activation-of-ampk-and-inhibits-hepatocellular-carcinoma-in-a-cdk4-6-independent-manner
#19
Feng-Shu Hsieh, Yao-Li Chen, Man-Hsin Hung, Pei-Yi Chu, Ming-Hsien Tsai, Li-Ju Chen, Yung-Jen Hsiao, Chih-Ting Shih, Mao-Ju Chang, Tzu-I Chao, Chung-Wai Shiau, Kuen-Feng Chen
Palbociclib, a CDK4/6 inhibitor, has recently been approved for hormone receptor-positive breast cancer patients. The effects of palbociclib as a treatment for other malignancies, including hepatocellular carcinoma (HCC), are of great clinical interest and are under active investigation. Here, we report the effects and a novel mechanism of action of palbociclib in HCC. We found that palbociclib induced both autophagy and apoptosis in HCC cells through a mechanism involving 5' AMP-activated protein kinase (AMPK) activation and protein phosphatase 5 (PP5) inhibition...
April 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28450156/microrna-7-impairs-autophagy-derived-pools-of-glucose-to-suppress-pancreatic-cancer-progression
#20
Dian-Na Gu, Ming-Jie Jiang, Zhu Mei, Juan-Juan Dai, Chen-Yun Dai, Chi Fang, Qian Huang, Ling Tian
Pancreatic cancer commonly addicts to aerobic glycolysis, and abnormally activates autophagy to adapt the stringent metabolic microenvironment. microRNA-7 (miR-7) was supposed to modulate various gastrointestinal cancer progression. We wonder whether miR-7 could destroy the reprogrammed metabolic homeostasis in pancreatic cancer via modulating the level of autophagy, and further affect tumor proliferation and survival. Herein, we first reported that pancreatic cancer could take advantage of autophagy as a survival strategy to provide essential glucose required for glycolysis metabolism...
April 25, 2017: Cancer Letters
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