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AMPK AND cancer

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https://www.readbyqxmd.com/read/28549345/a-novel-synthetic-derivative-of-quercetin-8-trifluoromethyl-3-5-7-3-4-o-pentamethyl-quercetin-inhibits-bladder-cancer-growth-by-targeting-the-ampk-mtor-signaling-pathway
#1
Ting Tao, Caimei He, Jun Deng, Yanjun Huang, Qiongli Su, Mei Peng, Meiling Yi, Kwame Oteng Darko, Hui Zou, Xiaoping Yang
Quercetin is a naturally existing compound and shows attractive anticancer properties for a variety of solid tumors including glioma, bladder cancer, hepatocellular carcinoma, breast cancer, hematological malignancies and prostate carcinoma. However, these anticancer properties have not been clinically approved due to unclear mechanistic information and its low bioactivity. In our previous study, we elucidated that quercetin activates AMPK pathway which is the major mechanism for its unique anticancer effect in bladder cancer...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549344/metformin-increases-chemo-sensitivity-via-gene-downregulation-encoding-dna-replication-proteins-in-5-fu-resistant-colorectal-cancer-cells
#2
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)...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545687/synergistic-effect-of-mek-inhibitor-and-metformin-combination-in-low-grade-serous-ovarian-cancer
#3
Ismail Mert, Jasdeep Chhina, Ghassan Allo, Jing Dai, Shelly Seward, Mark S Carey, Marta Llaurado, Shailendra Giri, Ramandeep Rattan, Adnan R Munkarah
OBJECTIVE: Low-grade serous ovarian cancer (LGSOC) constitutes 5-8% of epithelial ovarian cancers and is refractory to chemotherapy. We and others have shown metformin to cause significant growth inhibition in high-grade ovarian cancer both in vitro and in vivo. Here, we aimed to analyze if metformin was effective in inhibiting proliferation of LGSOC alone and in combination with MEK inhibitor. METHODS: Three LGSOC lines (VOA1056, VOA1312 and VOA5646) were treated with metformin, trametinib or 2-deoxyglucose (2DG) alone or in combination with metformin...
May 22, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28544264/ampk-%C3%AE-1-reduces-tumor-progression-and-improves-survival-in-p53-null-mice
#4
Vanessa P Houde, Sara Donzelli, Andrea Sacconi, Sandra Galic, Joanne A Hammill, Jonathan L Bramson, Robert A Foster, Theodoros Tsakiridis, Bruce E Kemp, Giuseppe Grasso, Giovanni Blandino, Paola Muti, Gregory R Steinberg
The AMP-activated protein kinase (AMPK) is a heterotrimeric protein complex that is an important sensor of cellular energy status. Reduced expression of the AMPK β1 isoform has been linked to reduced survival in different cancers but whether this accelerates tumor progression and the potential mechanism mediating these effects is not known. Further, it is unknown whether AMPK β1 is implicated in tumorigenesis and if so what tissues may be most sensitive. In the current study we find that in the absence of the tumor suppressor p53, germline genetic deletion of AMPK β1 accelerates the appearance of a T cell lymphoma that reduces lifespan compared to p53 deficiency alone...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28540163/dissecting-the-role-of-amp-activated-protein-kinase-in-human-diseases
#5
REVIEW
Jin Li, Liping Zhong, Fengzhong Wang, Haibo Zhu
AMP-activated protein kinase (AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes. Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type 2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere...
May 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#6
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28534931/leucine-rich-glioma-inactivated-3-integrative-analyses-support-its-role-in-the-cytokine-network
#7
Hyun A Kim, Nyoun Soo Kwon, Kwang Jin Baek, Dong-Seok Kim, Hye-Young Yun
Leucine-rich glioma inactivated (LGI)3 is a secreted protein member of LGI family. We previously repo-rted that LGI3 was upregulated in adipose tissues from obese mice and suppressed adipogenesis through its receptor, a disintegrin and metalloproteinase domain-containing protein 23 (ADAM23). We demonstrated that LGI3 regulated tumor necrosis factor-α and adiponectin, and proposed that LGI3 may be a pro-inflammatory adipokine involved in adipose tissue inflammation. In this study, we analyzed adipokine and cytokine profiles in LGI3 knockout mice and demonstrated that multiple factors were increased or decreased in the adipose tissues and plasma of the LGI3 knockout mice...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#8
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28529619/effects-of-prolonged-exposure-to-low-dose-metformin-in-thyroid-cancer-cell-lines
#9
Safar Kheder, Karen Sisley, Sirwan Hadad, Sabapathy P Balasubramanian
Background: Thyroid cancer is generally associated with an excellent prognosis, but there is significant long-term morbidity with standard treatment. Some sub-types however have a poor prognosis. Metformin, an oral anti-diabetic drug is shown to have anti-cancer effects in several types of cancer (breast, lung and ovarian cancer). The proposed mechanisms include activation of the Adenosine Mono-phosphate-activated Protein Kinase (AMPK) pathway and inhibition of the mTOR pathway (which promotes growth and proliferation)...
2017: Journal of Cancer
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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