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AMPK AND cancer

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https://www.readbyqxmd.com/read/28214826/emodin-increases-expression-of-insulin-like-growth-factor-binding-protein-1-through-activation-of-mek-erk-ampk%C3%AE-and-interaction-of-ppar%C3%AE-and-sp1-in-lung-cancer
#1
Qing Tang, JingJing Wu, Fang Zheng, Swei Sunny Hann, YuQing Chen
BACKGROUND: Emodin has anti-neoplastic activities on multiple tumors. However, the molecular mechanisms underlying this effect still remain to be fully understood. METHODS: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays and flow cytometry, respectively. Cell invasion and migration were examined by transwell invasion and wound healing assays. Western blot analysis was performed to examine the phosphorylation and protein expression of AMP-activated protein kinase alpha (AMPKα), extracellular signaling-regulated kinase 1/2 (ERK1/2), peroxisome proliferators-activated receptor gamma (PPARγ), insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and the transcription factor Sp1...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213701/ursolic-acid-mediated-changes-in-glycolytic-pathway-promote-cytotoxic-autophagy-and-apoptosis-in-phenotypically-different-breast-cancer-cells
#2
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Plant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5-20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)). UA-mediated response was more potent than BA-mediated response...
February 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28209925/the-stress-polarity-pathway-ampk-giv-es-protection-against-metabolic-insults
#3
Pradipta Ghosh
Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis...
February 15, 2017: Aging
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#4
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197628/resveratrol-induced-autophagy-and-apoptosis-in-cisplatin-resistant-human-oral-cancer-car-cells-a-key-role-of-ampk-and-akt-mtor-signaling
#5
Chao-Hsiang Chang, Chao-Ying Lee, Chi-Cheng Lu, Fuu-Jen Tsai, Yuan-Man Hsu, Je-Wei Tsao, Yu-Ning Juan, Hong-Yi Chiu, Jai-Sing Yang, Ching-Chiung Wang
Resveratrol is known to be an effective chemo-preventive phytochemical against multiple tumor cells. However, the increasing drug resistance avoids the cancer treatment in oral cavity cancer. In this study, we investigated the oral antitumor activity of resveratrol and its mechanism in cisplatin-resistant human oral cancer CAR cells. Our results demonstrated that resveratrol had an extremely low toxicity in normal oral cells and provoked autophagic cell death to form acidic vesicular organelles (AVOs) and autophagic vacuoles in CAR cells by acridine orange (AO) and monodansylcadaverine (MDC) staining...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28196954/metformin-and-thyroid-disease
#6
Xianghui Meng, Shuhang Xu, Guofang Chen, Michael Derwahl, Chao Liu
An intriguing area of research in thyroidology is the recently discovered association of insulin resistance with thyroid functional and morphological abnormalities. Individuals with hyperinsulinemia have larger thyroid gland and a higher prevalence of thyroid nodules and cancer. Accordingly, patients treated with metformin have a smaller thyroid volume and a lower risk of incident goiter, thyroid nodule and cancer. Multiple studies in vitro and in vivo have demonstrated that metformin can inhibit the growth of thyroid cells and different types of thyroid cancer cells by affecting the insulin/IGF-1 and mTOR pathways...
February 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28196589/an-oncogenic-role-for-the-ubiquitin-ligase-ube2o-by-targeting-ampk-%C3%AE-2-for-degradation
#7
D Grahame Hardie
There has been controversy regarding the role of AMPK in cancer, some of which may be due to functional differences between isoforms. In this issue of Cancer Cell, Vila et al. report that UBE2O, a ubiquitin ligase overexpressed in some human cancers, specifically triggers the ubiquitination and degradation of AMPK-α2.
February 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28191864/overexpression-of-nad-p-h-quinone-oxidoreductase-1-inhibits-hepatocellular-carcinoma-cell-proliferation-and-induced-apoptosis-by-activating-ampk-pgc-1%C3%AE-pathway
#8
Xin Zhang, Kun Han, Dong-Hong Yuan, Cun-Ying Meng
Hepatocellular carcinoma (HCC) is the most common lethal malignancy and a leading cause of malignancy-associated death in many countries, but mainly in Asia. Expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is involved in the growth of various human cancers, including HCC. NQO1 is considered an inhibitor of cancers. The present study aimed to investigate the function and mechanism of NQO1 in HCC. In this study, we found that NQO1 overexpression decreased HCC cell SK-hep-1 and Hep3B cell proliferation and induced apoptosis...
February 13, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28178338/the-impact-of-obesity-and-adiponectin-signaling-in-patients-with-renal-cell-carcinoma-a-potential-mechanism-for-the-obesity-paradox
#9
Ryuichi Ito, Shintaro Narita, Mingguo Huang, Taketoshi Nara, Kazuyuki Numakura, Koichiro Takayama, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi
Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this "obesity paradox" is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin...
2017: PloS One
https://www.readbyqxmd.com/read/28174693/fanconi-anemia-protein-fancd2-is-activated-by-aicar-a-modulator-of-ampk-and-cellular-energy-metabolism
#10
Min Jeong Chun, Hana Choi, Dong Wha Jun, Sunshin Kim, Yong-Nyun Kim, Soo-Youl Kim, Chang-Hun Lee
FANCD2 is a pivotal molecule in the pathogenesis of Fanconi anemia (FA), an autosomal recessive human syndrome with diverse clinical phenotypes, including cancer predisposition, short stature, and hematological abnormalities. In our previous study, we detected the functional association of FANC proteins, whose mutations are responsible for the onset of FA, with AMPK in response to DNA interstrand crosslinking lesions. Because AMPK is well known as a critical sensing molecule for cellular energy levels, we checked whether FANCD2 activation occurs after treatments affecting AMPK and/or cellular energy status...
February 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28170315/cytoplasmic-irradiation-induces-metabolic-shift-in-human-small-airway-epithelial-cells-via-activation-of-pim-1-kinase
#11
Jinhua Wu, Qin Zhang, Yen-Ruh Wuu, Sirui Zou, Tom K Hei
The unique cellular and molecular consequences of cytoplasmic damage caused by ionizing radiation were studied using a precision microbeam irradiator. Our results indicated that targeted cytoplasmic irradiation induced metabolic shift from an oxidative to glycolytic phenotype in human small airway epithelial cells (SAE). At 24 h postirradiation, there was an increase in the mRNA expression level of key glycolytic enzymes as well as lactate secretion in SAE cells. Using RNA-sequencing analysis to compare genes that were responsive to cytoplasmic versus nuclear irradiation, we found a glycolysis related gene, Pim-1, was significantly upregulated only in cytoplasmic irradiated SAE cells...
February 7, 2017: Radiation Research
https://www.readbyqxmd.com/read/28169991/a-spatiotemporal-hypothesis-for-the-regulation-role-and-targeting-of-ampk-in-prostate-cancer
#12
REVIEW
Ayesha S Khan, Daniel E Frigo
The 5'-AMP-activated protein kinase (AMPK) is a master regulator of cellular homeostasis. Despite AMPK's known function in physiology, its role in pathological processes such as prostate cancer is enigmatic. However, emerging evidence is now beginning to decode the paradoxical role of AMPK in cancer and, therefore, inform clinicians if - and how - AMPK could be therapeutically targeted. Spatiotemporal regulation of AMPK complexes could be one of the mechanisms that governs this kinase's role in cancer. We hypothesize that different upstream stimuli will activate select subcellular AMPK complexes...
February 1, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28161619/combination-of-metformin-with-chemotherapeutic-drugs-via-different-molecular-mechanisms
#13
REVIEW
Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits...
January 23, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28157701/metformin-treated-cancer-cells-modulate-macrophage-polarization-through-ampk-nf-%C3%AE%C2%BAb-signaling
#14
Chi-Fu Chiang, Ting-Ting Chao, Yu-Fu Su, Chia-Chen Hsu, Chu-Yen Chien, Kuo-Chou Chiu, Shine-Gwo Shiah, Chien-Hsing Lee, Shyun-Yeu Liu, Yi-Shing Shieh
Accumulating evidence is indicating metformin to possess the potential ability in preventing tumor development and suppressing cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. We found that metformin suppressed the ability of cancer to skew macrophage toward M2 phenotype. Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-α and attenuated M2-related cytokines IL-8, IL-10, and TGF-β expression. Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28154203/metformin-accumulation-correlates-with-organic-cation-transporter-2-protein-expression-and-predicts-mammary-tumor-regression-in-vivo
#15
L Allyson Checkley, Michael C Rudolph, Elizabeth A Wellberg, Erin D Giles, Reema S Wahdan-Alaswad, Julie A Houck, Susan Edgerton, Ann D Thor, Pepper Schedin, Steven Anderson, Paul MacLean
Several epidemiological studies have associated metformin treatment with a reduction in breast cancer incidence in pre-diabetic and type II diabetic populations. Uncertainty exists regarding which patient populations and/or tumor subtypes will benefit from metformin treatment, and most preclinical in vivo studies have given little attention to the cellular pharmacology of intratumoral metformin uptake. Epidemiological reports consistently link western-style high fat diets, which drive overweight and obesity, with increased risk of breast cancer...
February 2, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28152520/clinical-significance-and-effect-of-aeg-1-on-the-proliferation-invasion-and-migration-of-nsclc-a-study-based-on-immunohistochemistry-tcga-bioinformatics-in-vitro-and-in-vivo-verification
#16
Yu Zhang, Zu-Yun Li, Xin-Xi Hou, Xiao Wang, Yi-Huan Luo, Yan-Ping Ying, Gang Chen
BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is related to the tumorigenesis and deterioration of different cancers, including non-small cell lung cancer (NSCLC). However, the effect of AEG-1 in NSCLC remains unclear. In this study, we aimed to investigate the clinical significance and effect of AEG-1 on biological function of NSCLC. RESULTS: AEG-1 was significantly overexpressed in NSCLC tissues and closely correlated to the deterioration of NSCLC based on tissue microarray, TCGA database and meta-analysis...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28151470/adipocytes-activate-mitochondrial-fatty-acid-oxidation-and-autophagy-to-promote-tumor-growth-in-colon-cancer
#17
Yang-An Wen, Xiaopeng Xing, Jennifer W Harris, Yekaterina Y Zaytseva, Mihail I Mitov, Dana L Napier, Heidi L Weiss, B Mark Evers, Tianyan Gao
Obesity has been associated with increased incidence and mortality of a wide variety of human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate the metabolism of colon cancer cells remains elusive. In this study, we showed that adipocytes isolated from adipose tissues of colon cancer patients have an important role in modulating cellular metabolism to support tumor growth and survival. Abundant adipocytes were found in close association with invasive tumor cells in colon cancer patients...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28147319/mevastatin-blockade-of-autolysosome-maturation-stimulates-lbh589-induced-cell-death-in-triple-negative-breast-cancer-cells
#18
Zhaohu Lin, Zhuqing Zhang, Xiaoxiao Jiang, Xinhui Kou, Yong Bao, Huijuan Liu, Fanghui Sun, Shuang Ling, Ning Qin, Lan Jiang, Yonghua Yang
Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, and combining a HDACi with other agents is an attractive therapeutic strategy in solid tumors. We report here that mevastatin increases HDACi LBH589-induced cell death in triple-negative breast cancer (TNBC) cells. Combination treatment inhibited autophagic flux by preventing Vps34/Beclin 1 complex formation and downregulating prenylated Rab7, an active form of the small GTPase necessary for autophagosome-lysosome fusion. This means that co-treatment with mevastatin and LBH589 activated LKB1/AMPK signaling and subsequently inhibited mTOR...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28146060/adenosine-monophosphate-amp-activated-protein-kinase-a-new-target-for-nutraceutical-compounds
#19
REVIEW
Fabiola Marín-Aguilar, Luis E Pavillard, Francesca Giampieri, Pedro Bullón, Mario D Cordero
Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor which is activated by increases in adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio and/or adenosine diphosphate (ADP)/ATP ratio, and increases different metabolic pathways such as fatty acid oxidation, glucose transport and mitochondrial biogenesis. In this sense, AMPK maintains cellular energy homeostasis by induction of catabolism and inhibition of ATP-consuming biosynthetic pathways to preserve ATP levels...
January 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28119362/lkb1-expression-correlates-with-increased-survival-in-advanced-non-small-cell-lung-cancer-patients-treated-with-chemotherapy-and-bevacizumab
#20
Laura Bonanno, Angela De Paoli, Elisabetta Zulato, Giovanni Esposito, Fiorella Calabrese, Adolfo Favaretto, Antonio Santo, Alessandro Del Conte, Marco Chilosi, Francesco Oniga, Gabriella Sozzi, Massimo Moro, Francesco Ciccarese, Giorgia Nardo, Roberta Bertorelle, Cinzia Candiotto, Gian Luca De Salvo, Alberto Amadori, PierFranco Conte, Stefano Indraccolo
PURPOSE: LKB1 is a key sensor of metabolic stress, including hypoxia and glucose deprivation, two features of the tumor microenvironment exacerbated by antiangiogenic therapy. We investigated the role of LKB1 as potential predictive marker of sensitivity to bevacizumab in advanced non-small cell lung cancer (aNSCLC). EXPERIMENTAL DESIGN: We retrospectively analyzed LKB1 expression by immunohistochemistry in 98 samples out of 125 aNSCLC patients, including 59 patients treated with chemotherapy (CT) and 39 treated with CT plus bevacizumab...
January 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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