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AMPK AND cancer

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https://www.readbyqxmd.com/read/28924233/pharmacological-inhibition-of-camkk2-with-the-selective-antagonist-sto-609-regresses-nafld
#1
Brian York, Feng Li, Fumin Lin, Kathrina L Marcelo, Jianqiang Mao, Adam Dean, Naomi Gonzales, David Gooden, Suman Maity, Cristian Coarfa, Nagireddy Putluri, Anthony R Means
Binding of calcium to its intracellular receptor calmodulin (CaM) activates a family of Ca(2+)/CaM-dependent protein kinases. CaMKK2 (Ca(2+)/CaM-dependent protein kinase kinase 2) is a central member of this kinase family as it controls the actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK. CaMKK2 controls insulin signaling, metabolic homeostasis, inflammation and cancer cell growth highlighting its potential as a therapeutic target for a variety of diseases. STO-609 is a selective, small molecule inhibitor of CaMKK2...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923415/diindolylmethane-and-its-halogenated-derivatives-induce-protective-autophagy-in-human-prostate-cancer-cells-via-induction-of-the-oncogenic-protein-aeg-1-and-activation-of-amp-dependent-kinase-ampk
#2
Hossam Draz, Alexander A Goldberg, Vladimir I Titorenko, Emma Guns, Stephen H Safe, J Thomas Sanderson
3,3'-Diindolylmethane (DIM) and its synthetic halogenated derivatives 4,4'-Br2- and 7,7'-Cl2DIM (ring-DIMs) have recently been shown to induce protective autophagy in human prostate cancer cells. The mechanisms by which DIM and ring-DIMs induce autophagy have not been elucidated. As DIM is a mitochondrial ATP-synthase inhibitor, we hypothesized that DIM and ring-DIMs induce autophagy via alteration of intracellular AMP/ATP ratios and activation of AMPK signaling in prostate cancer cells. We found that DIM and ring-DIMs induced autophagy was accompanied by increased autophagic vacuole formation and conversion of LC3BI to LC3BII in LNCaP and C42B human prostate cancer cells...
September 15, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28915708/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
#3
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915611/metformin-increases-chemo-sensitivity-via-gene-downregulation-encoding-dna-replication-proteins-in-5-fu-resistant-colorectal-cancer-cells
#4
Sung-Hee Kim, Soon-Chan Kim, Ja-Lok Ku
Metformin is most widely prescribed for type 2 diabetes. Recently, evidences have shown that metformin has anticancer effects on pancreatic-, colorectal-, ovarian-, and other cancers. Because metformin has less adverse effects and is inexpensive, it could be a useful chemo-therapeutic agent with anticancer effects. In this study, we demonstrated metformin inhibited by cell proliferation, cell migration ability, clonogenic ability, and cancer stem cell population. Metformin also induced cell cycle arrest in parental-(SNU-C5), and 5-Fu resistant-colorectal cancer cell line (SNU-C5_5FuR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912888/sulforaphane-induced-cell-cycle-arrest-and-senescence-are-accompanied-by-dna-hypomethylation-and-changes-in-microrna-profile-in-breast-cancer-cells
#5
Anna Lewinska, Jagoda Adamczyk-Grochala, Anna Deregowska, Maciej Wnuk
Cancer cells are characterized by genetic and epigenetic alterations and phytochemicals, epigenetic modulators, are considered as promising candidates for epigenetic therapy of cancer. In the present study, we have investigated cancer cell fates upon stimulation of breast cancer cells (MCF-7, MDA-MB-231, SK-BR-3) with low doses of sulforaphane (SFN), an isothiocyanate. SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence, whereas at the concentration of 20 µM, apoptosis was induced...
2017: Theranostics
https://www.readbyqxmd.com/read/28906486/small-molecule-rl71-triggered-excessive-autophagic-cell-death-as-a-potential-therapeutic-strategy-in-triple-negative-breast-cancer
#6
Jian Gao, Minmin Fan, Shuang Peng, Minxia Zhang, Gang Xiang, Xin Li, Wenjie Guo, Yang Sun, Xuefeng Wu, Xudong Wu, Guang Liang, Yan Shen, Qiang Xu
Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor prognosis owing to the high propensity for metastatic progression and the absence of specific targeted treatment. Here, we revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2) exhibited potent anti-cancer activity on all TNBC cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca(2+) from the endoplasmic reticulum (ER) into the cytosol by inhibiting SERCA2 activity...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28900501/metformin-sensitizes-leukemia-cells-to-vincristine-via-activation-of-amp-activated-protein-kinase
#7
Yong Yi, Linfeng Gao, Min Wu, Juan Ao, Chunyan Zhang, Xiaodong Wang, Min Lin, Johann Bergholz, Yujun Zhang, Zhi-Xiong Jim Xiao
Vincristine is extensively used chemotherapeutic medicine to treat leukemia. However, it remains a critical clinical problem with regard to its toxicity and drug-resistance. AMP-activated protein kinase (AMPK) is an energy sensor that is pivotal in maintaining cell metabolic homeostasis. It is reported that AMPK is involved in vincristine-induced apoptosis. However, whether AMPK is involved in chemotherapy-resistance is largely unclear. It is well-documented that metformin, a widely used medicine to treat type II diabetes, possesses anti-cancer activities, yet whether metformin affects leukemia cell viability via vincristine is unknown...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28881794/enhanced-efficacy-of-akt-and-fak-kinase-combined-inhibition-in-squamous-cell-lung-carcinomas-with-stable-reduction-in-pten
#8
Andrea Cavazzoni, Silvia La Monica, Roberta Alfieri, Andrea Ravelli, Nele Van Der Steen, Rocco Sciarrillo, Denise Madeddu, Costanza Anna Maria Lagrasta, Federico Quaini, Mara Bonelli, Claudia Fumarola, Daniele Cretella, Graziana Digiacomo, Marcello Tiseo, Godefridus J Peters, Andrea Ardizzoni, Pier Giorgio Petronini, Elisa Giovannetti
Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and amplification, AKT mutations and loss or reduced PTEN expression. Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878670/daf-16-foxo-transcription-factor-in-aging-and-longevity
#9
REVIEW
Xiaojuan Sun, Wei-Dong Chen, Yan-Dong Wang
Aging is associated with age-related diseases and an increase susceptibility of cancer. Dissecting the molecular mechanisms that underlie aging and longevity would contribute to implications for preventing and treating the age-dependent diseases or cancers. Multiple signaling pathways such as the insulin/IGF-1 signaling pathway, TOR signaling, AMPK pathway, JNK pathway and germline signaling have been found to be involved in aging and longevity. And DAF-16/FOXO, as a key transcription factor, could integrate different signals from these pathways to modulate aging, and longevity via shuttling from cytoplasm to nucleus...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28877685/positive-regulation-of-prostate-cancer-cell-growth-by-lipid-droplet-forming-and-processing-enzymes-dgat1-and-abhd5
#10
Ranjana Mitra, Thuc T Le, Priyatham Gorjala, Oscar B Goodman
BACKGROUND: Neoplastic cells proliferate rapidly and obtain requisite building blocks by reprogramming metabolic pathways that favor growth. Previously, we observed that prostate cancer cells uptake and store lipids in the form of lipid droplets, providing building blocks for membrane synthesis, to facilitate proliferation and growth. Mechanisms of lipid uptake, lipid droplet dynamics and their contribution to cancer growth have yet to be defined. This work is focused on elucidating the prostate cancer-specific modifications in lipid storage pathways so that these modified gene products can be identified and therapeutically targeted...
September 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28876465/procyanidin-b2-3-3-di-o-gallate-induces-oxidative-stress-mediated-cell-death-in-prostate-cancer-cells-via-inhibiting-map-kinase-phosphatase-activity-and-activating-erk1-2-and-ampk
#11
Rahul Kumar, Gagan Deep, Michael F Wempe, Joseph Surek, Amit Kumar, Rajesh Agarwal, Chapla Agarwal
Neoplastic cells exhibit higher oxidative stress compared to normal cells; however, antioxidants based clinical trials have mostly failed. Another attractive therapeutic approach is to further increase the oxidative stress in cancer cells leading to cell death. Herein, we show that Procyanidin B2 3,3"-di-O-gallate (B2G2), the most active constituent of grape seed extract, treatment causes cell death in human prostate cancer (PCa) cells (LNCaP and 22Rv1) via increasing the reactive oxygen species (ROS) generation...
September 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28875849/modulation-of-both-insulin-resistance-and-cancer-growth-by-inositol
#12
Mariano Bizzarri, Simona Dinicola, Alessandra Cucina
Insulin resistance indicates a deregulated set of biochemical pathways and physiological functions involved in the pathogenesis of a number of diseases, including type 2 diabetes and cancer. Conversely, a number of synthetic and natural insulin sensitizers, including inositol, have been recognized to exert both anti-diabetic as well as anti-cancer properties. Inositol participates in insulin transduction signaling, and deregulated inositol metabolism has been ascertained in several conditions associated with insulin resistance...
August 30, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28871429/elucidating-the-rapid-action-of-2-2-chlorophenyl-ethylbiguanide-on-ht-29-cells-under-a-serum-and-glucose-deprived-condition
#13
Kentaro Oh-Hashi, Shiori Matsumoto, Takayuki Sakai, Yuki Nomura, Kensuke Okuda, Hideko Nagasawa, Yoko Hirata
We recently demonstrated the cytotoxic action of a novel phenformin derivative, 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on HT-29 cells under a serum- and glucose-deprived condition. In that study, we showed that the ATF6 arm of the ER stress pathway and c-Myc expression were downregulated 12 h after the treatment with 2-Cl-Phen. Through characterization of intracellular events at the early phase of the 2-Cl-Phen treatment before noticeable morphological changes, we found rapid fluctuations in the c-Myc and ATF4 proteins but not in their mRNAs in 2-Cl-Phen-treated HT-29 cells under the serum- and glucose-deprived condition...
September 5, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28870914/an-adaptation-system-to-avoid-apoptosis-via-autophagy-under-hypoxic-conditions-in-pancreatic-cancer-cells
#14
Satoshi Owada, Kanako Ito, Hitoshi Endo, Yukari Shida, Chisa Okada, Takahiro Nezu, Masayuki Tatemichi
BACKGROUND/AIM: Pancreatic cancer tissue is a hypoxic environment resistant to anticancer drugs. This study examined the role of autophagy as a response to hypoxic stress in pancreatic cancer. MATERIALS AND METHODS: Pancreatic cell lines (PANC-1, BxPC-3 and AsPC-1) were exposed to hypoxic conditions using cobalt chloride, a hypoxia-mimicking agent. Protein expression and cytotoxicity assays were performed to determine the effect of hypoxia on autophagy. RESULTS: When pancreatic cancer cells were exposed to hypoxia, autophagy was induced...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28867797/flavonoid-rich-extract-of-paulownia-fortunei-flowers-attenuates-diet-induced-hyperlipidemia-hepatic-steatosis-and-insulin-resistance-in-obesity-mice-by-ampk-pathway
#15
Chanmin Liu, Jieqiong Ma, Jianmei Sun, Chao Cheng, Zhaojun Feng, Hong Jiang, Wei Yang
The flavonoid-rich extract from Paulownia fortunei flowers (EPF) has been reported to prevent obesity and other lipid metabolism disease. However, the mechanism of its protective effects is not yet clear. The objective of this study was to investigate molecular factors involved in the hypoglycemic and hypolipidemic effects of EPF in obese mice fed a high-fat diet (HFD). Male h ICR (Institute of Cancer Research) mice were fed a HFD containing or not containing the EPF (50 or 100 mg/kg) for eight weeks. EPF reduced body weight gain, lipid accumulation in livers and levels of lipid, glucose and insulin in plasma as well as reduced insulin resistance as compared with the HFD group...
August 30, 2017: Nutrients
https://www.readbyqxmd.com/read/28856747/anticancer-effects-of-a-korean-herbal-medicine-formula-h9-via-ampk-and-her2-pi3k-akt-signaling-in-breast-cancer-cells
#16
Ju-Hee Lee, Young Hoon Son, Young-Won Kwon, Sung Yun Park, Byung-Soo Koo, Seung Hyun Jung
An H9 is a formula of nine medicinal herbs derived from Osuyubujaijung-tang, a traditional Korean prescription for Soeumin constitution. In our previous study, H9 showed anticancer effects against breast cancer and non-small-cell lung cancer. However, the underlying mechanisms of these effects have not yet been elucidated. In this study, we investigated the effects of H9, both alone and in combination with trastuzumab, on breast cancer cells and sought to elucidate the mechanisms involved. H9 suppressed the proliferation of human breast cancer cells, induced arrest of the cell cycle at the G0/G1 phase, and caused mitochondrial dysfunction and apoptosis...
August 30, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28854356/multilayered-reprogramming-in-response-to-persistent-dna-damage-in-c-%C3%A2-elegans
#17
Diletta Edifizi, Hendrik Nolte, Vipin Babu, Laia Castells-Roca, Michael M Mueller, Susanne Brodesser, Marcus Krüger, Björn Schumacher
DNA damage causally contributes to aging and age-related diseases. Mutations in nucleotide excision repair (NER) genes cause highly complex congenital syndromes characterized by growth retardation, cancer susceptibility, and accelerated aging in humans. Orthologous mutations in Caenorhabditis elegans lead to growth delay, genome instability, and accelerated functional decline, thus allowing investigation of the consequences of persistent DNA damage during development and aging in a simple metazoan model. Here, we conducted proteome, lipidome, and phosphoproteome analysis of NER-deficient animals in response to UV treatment to gain comprehensive insights into the full range of physiological adaptations to unrepaired DNA damage...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28853207/curcumin-ameliorates-severe-influenza-pneumonia-via-attenuating-lung-injury-and-regulating-macrophage-cytokines-production
#18
Shuguang Han, Jing Xu, Xiangjun Guo, Mao Huang
Curcumin, an active phenolic agent extract from the Curcuma longa, exhibits excellent anti-cancer, anti-inflammation, and neuroprotective effects. We aimed to investigate the anti-influenza role of Curcumin in vitro and in vivo. The effect of Curcumin on replication of influenza A virus (IAV) was examined in human lung cancer cell line A549, as well as in a mouse model. Curcumin could inhibit IAV in vitro and alleviate the severity of the disease in the mouse after infection with IAV. The results also indicated that Curcumin could trigger expression of Heme oxygenase-1 in vivo and attenuate IAV-induced injury to the lung tissue...
August 29, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28842631/elucidation-of-dietary-polyphenolics-as-potential-inhibitor-of-microtubule-affinity-regulating-kinase-4-in-silico-and-in-vitro-studies
#19
Parvez Khan, Shafikur Rahman, Aarfa Queen, Saaliqa Manzoor, Farha Naz, Gulam Mustafa Hasan, Suaib Luqman, Jihoe Kim, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase belonging to AMPK-like family, has recently become an important drug target against cancer and neurodegenerative disorders. In this study, we have evaluated different natural dietary polyphenolics including rutin, quercetin, ferulic acid, hesperidin, gallic acid and vanillin as MARK4 inhibitors. All compounds are primarily binds to the active site cavity of MARK4. In silico observations were further complemented by the fluorescence-binding studies and isothermal titration calorimetry (ITC) measurements...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835570/amp-activated-protein-kinase-a-therapeutic-target-in-intestinal-diseases
#20
REVIEW
Xiaofei Sun, Mei-Jun Zhu
Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a highly conserved energy sensor, has a crucial role in cardiovascular, neurodegenerative and inflammatory diseases, as well as in cancer and metabolic disorders. Accumulating studies have demonstrated that AMPK activation enhances paracellular junctions, nutrient transporters, autophagy and apoptosis, and suppresses inflammation and carcinogenesis in the intestine, indicating an essential role of AMPK in intestinal health. AMPK inactivation is an aetiological factor in intestinal dysfunctions...
August 2017: Open Biology
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