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AMPK AND cancer

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https://www.readbyqxmd.com/read/29340974/inhibiting-6-phosphogluconate-dehydrogenase-selectively-targets-breast-cancer-through-ampk-activation
#1
Xiaoyu Yang, Xiaochun Peng, Jiangrong Huang
PURPOSE: 6-phosphogluconate dehydrogenase (6PGD), a key enzyme of the oxidative pentose phosphate pathway, is involved in tumor growth and metabolism. Although high 6PGD activity has been shown to be associated with poor prognosis, its role and therapeutic value in breast cancer remain unknown. METHODS: The levels and roles of 6PGD were analyzed in breast cancer cells and their normal counterparts. The underlying mechanisms of 6PGD's roles are also analyzed. RESULTS: We found that 6PGD is aberrantly activated in breast cancer as shown by its increased transcriptional and translational levels as well as enzyme activity in breast cancer tissues and cell lines compared to normal counterparts...
January 16, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29340030/increased-efficacy-of-metformin-corresponds-to-differential-metabolic-effects-in-the-ovarian-tumors-from-obese-versus-lean-mice
#2
Jianjun Han, Weiya Z Wysham, Yan Zhong, Hui Guo, Lu Zhang, Kim M Malloy, Hallum K Dickens, Gene Huh, Douglas Lee, Liza Makowski, Chunxiao Zhou, Victoria L Bae-Jump
Obesity is a significant risk factor for ovarian cancer (OC) and associated with worse outcomes for this disease. We assessed the anti-tumorigenic effects of metformin in human OC cell lines and a genetically engineered mouse model of high grade serous OC under obese and lean conditions. Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of apoptosis, reduction of invasion and decreased hTERT expression...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339542/ampk-akt-double-negative-feedback-loop-in-breast-cancer-cells-regulates-their-adaptation-to-matrix-deprivation
#3
Manipa Saha, Saurav Kumar, Shoiab Bukhari, Sai A Balaji, Prashant Kumar, Sravanth K Hindupur, Annapoorni Rangarajan
Cell detachment from the extracellular matrix triggers anoikis. Disseminated tumor cells must adapt to survive matrix deprivation, while still retaining the ability to attach at secondary sites and re-initiate cell division. In this study, we illuminate mechanisms that enable reversible matrix attachment by breast cancer cells. Matrix deprival triggered AMPK activity and concomitantly inhibited AKT activity by upregulating the AKT phosphatase PHLPP2. The resultant pAMPKhigh/pAKTlow state was critical for cell survival in suspension, as PHLPP2 silencing also increased anoikis while impairing autophagy and metastasis...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29336118/resveratrol-potently-counteracts-quercetin-starvation-induced-autophagy-and-sensitizes-hepg2-cancer-cells-to-apoptosis
#4
Sarah Tomas-Hernández, Jordi Blanco, Cristina Rojas, Joel Roca-Martínez, María José Ojeda-Montes, Raúl Beltrán-Debón, Santiago Garcia-Vallve, Gerard Pujadas, Lluís Arola, Miquel Mulero
SCOPE: Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells METHODS AND RESULTS: Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining...
January 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29333122/metformin-enhanced-in-vitro-radiosensitivity-associates-with-g2-m-cell-cycle-arrest-and-elevated-adenosine-5-monophosphate-activated-protein-kinase-levels-in-glioblastoma
#5
Sebastian Adeberg, Denise Bernhardt, Semi B Harrabi, Nils H Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus, Stefan Rieken
Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29330052/esco2-knockdown-inhibits-cell-proliferation-and-induces-apoptosis-in-human-gastric-cancer-cells
#6
Hongmei Chen, Lei Zhang, Wenting He, Liu Tao, Yang Zhao, Hao Chen, Yumin Li
Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion regulation and genomic stability, has not been studied in human gastric cancer (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited cell proliferation and induced cell apoptosis in vitro and suppressed tumor xenograft development in vivo. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) was activated following the suppression of its downstream targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 1 (p70S6K1), and this result was consistent with p53 activation...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29328363/support-vector-machine-classifier-for-prediction-of-the-metastasis-of-colorectal-cancer
#7
Jiajun Zhi, Jiwei Sun, Zhongchuan Wang, Wenjun Ding
Colorectal cancer (CRC) is one of the most common cancers and a major cause of mortality. The present study aimed to identify potential biomarkers for CRC metastasis and uncover the mechanisms underlying the etiology of the disease. The five datasets GSE68468, GSE62321, GSE22834, GSE14297 and GSE6988 were utilized in the study, all of which contained metastatic and non-metastatic CRC samples. Among them, three datasets were integrated via meta-analysis to identify the differentially expressed genes (DEGs) between the two types of samples...
January 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29323154/effects-of-metformin-on-colorectal-cancer-stem-cells-depend-on-alterations-in-glutamine-metabolism
#8
Jae Hyun Kim, Kyoung Jin Lee, Yoojeong Seo, Ji-Hee Kwon, Jae Pil Yoon, Jo Yeon Kang, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Ii Kim
Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29312618/estrogen-receptor-signaling-mediates-leptin-induced-growth-of-breast-cancer-cells-via-autophagy-induction
#9
Pawan Kumar Raut, Dong Young Choi, Sang Hyun Kim, Jin Tae Hong, Taeg Kyu Kwon, Jee Heon Jeong, Pil-Hoon Park
Leptin, a hormone derived from adipose tissue, promotes growth of cancer cells via multiple mechanisms. Estrogen receptor signaling is also known to stimulate the growth of breast cancer cells. However, the involvement of estrogen receptor signaling in the oncogenic actions of leptin and its underlying mechanisms are not clearly understood. Herein, we investigated mechanisms for estrogen receptor signaling-mediated growth of breast cancer cells, particularly focusing on autophagy, which plays a crucial role in leptin-induced tumor growth...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29307823/autophagy-mediated-upregulation-of-cytoplasmic-claudin-1-stimulates-the-degradation-of-sqstm1-p62-under-starvation
#10
Jaewhan Kim, Sunkyung Choi, Jong Ok Kim, Kee K Kim
Claudin 1, a major tight junction protein, is highly expressed in various types of tumors such as thyroid, breast, and colorectal cancers. Moreover, claudin 1 is frequently found in the cytoplasm in various types of tumor cells. However, the cytoplasmic function of claudin 1 in tumors still remains largely unknown. Here, we investigated the novel function of cytoplasmic claudin 1 in autophagy. The mRNA expression level of claudin 1 was higher in several types of tumors than in normal tissues. Furthermore, colon tumor tissues showed increased autophagy compared with the adjacent normal tissues...
January 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29305864/fenofibrate-inhibits-mtor-p70s6k-signaling-and-simultaneously-induces-cell-death-in-human-prostate-cancer-cells
#11
Xin Lian, Junlian Gu, Baoshan Gao, Yan Li, Chendil Damodaran, Wei Wei, Yaowen Fu, Lu Cai
Fenofibrate is the most widely used lipid-lowering drug, but it seems to have anti-tumor effects in several tumor cell lines. However, there are only a few reports on its effects on human prostate cancer cells. Thus, we investigated the anti-proliferative effects of fenofibrate on human prostate cancer cells and potential mechanisms. The methods used include cell viability analysis with an MTT assay, as well as apoptosis and related signaling pathway analyses with flow cytometry and Western blotting. Fenofibrate inhibited PC-3 cell growth in dose- and time-dependent manners...
January 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29299159/lactate-activated-macrophages-induced-aerobic-glycolysis-and-epithelial-mesenchymal-transition-in-breast-cancer-by-regulation-of-ccl5-ccr5-axis-a-positive-metabolic-feedback-loop
#12
Sensen Lin, Li Sun, Xiaodan Lyu, Xiongfei Ai, Danyu Du, Nan Su, Hongyang Li, Luyong Zhang, Jun Yu, Shengtao Yuan
Aberrant energy metabolism is critical for cancer progression. Tumor-associated macrophages (TAMs) can stimulate tumor angiogenesis and enhance cancer metastasis; however, the metabolic interaction between cancer cells and macrophages characterized by lactate shuttles remains unclear. Here, we showed that lactate activated human macrophages to a TAM-like phenotype and stimulated the secretion of CCL5 by activation of Notch signaling in macrophages. Reciprocally, CCL5 increased cell migration, induced cancer cell EMT, and promoted aerobic glycolysis in breast cancer cells, suggesting a positive metabolic feedback loop in the co-culture system...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295560/fascaplysin-sensitizes-anti-cancer-effects-of-drugs-targeting-akt-and-ampk
#13
Taek-In Oh, Jun Ho Lee, Seongman Kim, Taek-Jin Nam, Young-Seon Kim, Byeong Mo Kim, Woo Jong Yim, Ji-Hong Lim
Fascaplysin, a natural product isolated from marine sponges, is a potential candidate for the development of anti-cancer drugs. However, the mechanism underlying its therapeutic effect of strengthening anti-cancer efficacy of other drugs is poorly understood. Here, we found that fascaplysin increases phosphorylation of protein kinase B (PKB), also known as AKT, and adenosine monophosphate-activated protein kinase (AMPK), which are considered therapeutic targets for cancer treatment due to their anti-apoptotic or pro-survival functions in cancer...
December 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29290796/prlz-increases-prostate-cancer-docetaxel-resistance-by-inhibiting-lkb1-ampk-mediated-autophagy
#14
Jin Zeng, Wei Liu, Yi-Zeng Fan, Da-Lin He, Lei Li
Rationale: Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...
2018: Theranostics
https://www.readbyqxmd.com/read/29288670/the-suppressive-effects-of-britannin-bri-on-human-liver-cancer-through-inducing-apoptosis-and-autophagy-via-ampk-activation-regulated-by-ros
#15
Yong-Qiang Cui, Yan-Jun Liu, Fan Zhang
Britannin (Bri), isolated from Inula aucheriana, is a sesquiterpene lactone (SL), a class of secondary metabolites. Previous studies have suggested the anti-cancer potential of Bri; however, the molecular mechanism remains elusive. The present study investigated the effects of Bri on liver cancer progression. Our findings indicated that Bri significantly suppressed the growth of liver cancer cell lines. Mechanistic researches revealed that Bri induced apoptosis through the extrinsic and intrinsic apoptotic pathways, as evidenced by the increase of Caspase-8, -9 and -3 cleavages...
December 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29285837/the-new-metformin-derivative-hl156a-prevents-oral-cancer-progression-by-inhibiting-the-igf-akt-mtor-pathways
#16
Thuy Giang Lam, Yun Soo Jeong, Soo-A Kim, Sang-Gun Ahn
Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of this study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose dependent manner. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced ROS levels and apoptotic cells with caspase-3 and -9 activation...
December 29, 2017: Cancer Science
https://www.readbyqxmd.com/read/29284117/knockdown-of-ampk%C3%AE-decreases-atm-expression-and-increases-radiosensitivity-under-hypoxia-and-nutrient-starvation-in-an-sv40-transformed-human-fibroblast-cell-line-lm217
#17
Yasuhiko Murata, Takuma Hashimoto, Yusuke Urushihara, Soichiro Shiga, Kazuya Takeda, Keiichi Jingu, Yoshio Hosoi
BACKGROUND: Presence of unperfused regions containing cells under hypoxia and nutrient starvation contributes to radioresistance in solid human tumors. It is well known that hypoxia causes cellular radioresistance, but little is known about the effects of nutrient starvation on radiosensitivity. We have reported that nutrient starvation induced decrease of mTORC1 activity and decrease of radiosensitivity in an SV40-transformed human fibroblast cell line, LM217, and that nutrient starvation induced increase of mTORC1 activity and increase of radiosensitivity in human liver cancer cell lines, HepG2 and HuH6 (Murata et al...
December 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29282893/autophagy-novel-applications-of-nonsteroidal-anti-inflammatory-drugs-for-primary-cancer
#18
REVIEW
Chen Yu, Wei-Bing Li, Jun-Bao Liu, Jian-Wei Lu, Ji-Feng Feng
In eukaryotic cells, autophagy is a process associated with programmed cell death. During this process, cytoplasmic proteins and organelles are engulfed by double-membrane autophagosomes, which then fuse with lysosomes to form autolysosomes. These autolysosomes then degrade their contents to recycle the cellular components. Autophagy has been implicated in a wide variety of physiological and pathological processes that are closely related to tumorigenesis. In recent years, an increasing number of studies have indicated that nonsteroidal anti-inflammatory drugs, such as celecoxib, meloxicam, sulindac, aspirin, sildenafil, rofecoxib, and sodium salicylate, have diverse effects in cancer that are mediated by the autophagy pathway...
December 28, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29275212/nrf2-facilitates-breast-cancer-cell-growth-via-hif1%C3%A9-mediated-metabolic-reprogramming
#19
Hong-Sheng Zhang, Guang-Yuan Du, Zhong-Guo Zhang, Zhen Zhou, Hong-Liang Sun, Xiao-Ying Yu, Yu-Ting Shi, Dan-Ning Xiong, Hu Li, Ying-Hui Huang
High aerobic glycolysis not only provides energy to breast cancer cells, but also supports their anabolic growth. The redox sensitive transcription factor NRF2 is over-expressed in multiple cancers, including breast cancer. It is unclear whether NRF2 could promote breast cancer cell growth through enhancing glycolysis. In this study, we found that NRF2 and HIF1α mRNA and protein levels were significantly increased in MCF-7 and MDA-MB-231 breast cancer cells as compared to MCF-10A benign breast epithelial cells...
December 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29273065/curcumin-synergizes-with-5-fluorouracil-by-impairing-ampk-ulk1-dependent-autophagy-akt-activity-and-enhancing-apoptosis-in-colon-cancer-cells-with-tumor-growth-inhibition-in-xenograft-mice
#20
Pan Zhang, Ze-Lin Lai, Hui-Fen Chen, Min Zhang, An Wang, Tao Jia, Wen-Qin Sun, Xi-Min Zhu, Xiao-Feng Chen, Zheng Zhao, Jun Zhang
BACKGROUND: Chemoresistance is a major obstacle that limits the benefits of 5-Fluorouracil (5-Fu)-based chemotherapy for colon cancer patients. Autophagy is an important cellular mechanism underlying chemoresistance. Recent research advances have given new insights into the use of natural bioactive compounds to overcome chemoresistance in colon cancer chemotherapy. As one of the multitargeted and safer phytomedicines, curcumin has been reported to work as cancer-specific chemosensitizer, presumably via induction of autophagic signaling pathways...
December 22, 2017: Journal of Experimental & Clinical Cancer Research: CR
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