Read by QxMD icon Read

Fasn inhibitors

Laura Galbraith, Hing Y Leung, Imran Ahmad
The link between prostate cancer (PC) development and lipid metabolism is well established, with AR intimately involved in a number of lipogenic processes involving SREBP1, PPARG, FASN, ACC, ACLY and SCD1. Recently, there is growing evidence implicating the role of obesity and peri-prostatic adipose tissue (PPAT) in PC aggressiveness and related mortality, suggesting the importance of lipid pathways in both localised and disseminated disease. A number of promising agents are in development to target the lipogenic axis in PC, and the likelihood is that these agents will form part of combination drug strategies, with targeting of multiple metabolic pathways (e...
February 18, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Richard G Carroll, Zbigniew Zaslona, Silvia Galván-Peña, Emma L Koppe, Daniel C Sévin, Stefano Angiari, Martha Triantafilou, Kathy Triantafilou, Louise K Modis, Luke O'Neill
Different immune activation states require distinct metabolic features and activities in immune cells. For instance, inhibition of fatty acid synthase (FASN), which catalyzes the synthesis of long-chain fatty acids, prevents the proinflammatory response in macrophages; however, the precise role of this enzyme in this response remains poorly defined. Consistent with previous studies, we found here that FASN is essential for lipopolysaccharide-induced, Toll-like receptor (TLR)-mediated macrophage activation. Interestingly, only agents that block FASN upstream of acetoacetyl-CoA synthesis, including the well-characterized FASN inhibitor C75, inhibited TLR4 signaling, while those acting downstream had no effect...
February 20, 2018: Journal of Biological Chemistry
Bao-Long Pan, Zong-Wu Tong, Ling Wu, Li Pan, Jun-E Li, You-Guang Huang, Shu-De Li, Shi-Xun Du, Xu-Dong Li
BACKGROUND/AIMS: This study aimed to investigate the mechanism by which microRNA-206 (miR-206) affects the proliferation, apoptosis, migration and invasion of osteosarcoma (OS) cells by targeting ANXA2 via the AKT signaling pathway. METHODS: A total of 132 OS tissues and 120 osteochondroma tissues were examined in this study. The targeting relationship between miR-206 and ANXA2 was verified with a dual-luciferase reporter assay. The miR-206 expression and ANXA2, AKT, PARP, FASN, Survivin, Bax, Mcl-1 and Bcl-1 mRNA and protein expression in the above two groups were examined by qRT-PCR and western blotting...
February 15, 2018: Cellular Physiology and Biochemistry
Azhar Ali, Elena Levantini, Jun Ting Teo, Julian Goggi, John G Clohessy, Chan Shuo Wu, Leilei Chen, Henry Yang, Indira Krishnan, Olivier Kocher, Junyan Zhang, Ross A Soo, Kishore Bhakoo, Tan Min Chin, Daniel G Tenen
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug...
February 15, 2018: EMBO Molecular Medicine
Shanshan Zhang, Xiaoxing Li, Hui-Yun Wang, X F Steven Zheng
MAF1 was discovered as a master repressor of Pol III-dependent transcription in response to diverse extracellular signals, including growth factor, nutrient and stress. It is regulated through posttranslational mechanisms such as phosphorylation. A prominent upstream regulator of MAF1 is the mechanistic target of rapamycin (mTOR) pathway. mTOR kinase directly phosphorylates MAF1, controlling its localization and transcriptional activity. In mammals, MAF1 has also been shown to regulate Pol I- and Pol II-dependent transcription...
January 30, 2018: Biochimica et Biophysica Acta
Wanwan Zhu, Chunmei Lv, Jiao Wang, Qiang Gao, Hui Zhu, Haixia Wen
Fatty acid synthase (FASN) is a key enzyme involved in fatty acid biosynthesis and serves an important role in breast cancer development. The aim of the present study was to investigate the effects of patuletin on the gene expression and activity of FASN in the human breast cancer SK-BR-3 cell line, and the apoptotic effects of patuletin to breast cancer cells. Quantitative reverse transcription polymerase chain reaction, western blotting and intracellular FASN activity assays were used to evaluate FASN gene expression, protein expression and activity in patuletin-treated SK-BR-3 cells...
December 2017: Oncology Letters
MingJing Shen, Ying Tsai, Rongying Zhu, Peter C Keng, Yongbing Chen, Yuhchyau Chen, Soo Ok Lee
Cisplatin remains the most effective therapy for non-small cell lung cancer (NSCLC). We previously have found cisplatin-resistant lung cancer cells (A549CisR and H157CisR) were more resistant to natural killer (NK) cell-mediated cytotoxicity than parental cells. We also discovered that fatty acid synthase (FASN) levels in cisplatin-resistant cells were significantly higher than parental cells. To reveal whether a link exists between the up-regulated FASN levels and higher resistance to NK cell cytotoxicity, we performed inhibition studies using a FASN inhibitor and applied the FASN knockdown approach...
January 3, 2018: Biochimica et Biophysica Acta
Mina Kim, Hae-Ahm Lee, Hyun-Min Cho, Seol-Hee Kang, Eunjo Lee, In Kyeom Kim
Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0...
January 2018: Korean Journal of Physiology & Pharmacology
Li-Hsuan Huang, Hsin-Yun Chung, Hui-Min Su
BACKGROUND: Fatty acid synthase (FASN), the major enzyme in de novo fatty acid synthesis, is highly expressed in breast cancer and its expression is reduced by polyunsaturated fatty acids (PUFAs) in liver. We previously found a positive association between rat mammary tumor levels of the n-6 PUFA arachidonic acid (AA) and tumor weight. We examined the roles of the major n-3 PUFA, docosahexaenoic acid (DHA, 22:6n-3), and the major n-6 PUFA, AA, in FASN expression in, and proliferation of, human breast cancer MCF-7 cells...
December 28, 2017: BMC Cancer
Tingting Chen, Lan Zhou, Hua Li, Yuan Tian, Junqin Li, Lihua Dong, Yuhua Zhao, Dapeng Wei
The aim of the present study was to investigate changes in the expression of ErbBs during epithelial-mesenchymal transition (EMT) of breast cancer cells and its association with the expression of fatty acid synthase (FASN). MCF-7-MEK5 cells were used as the experimental model, while MCF-7 cells were used as a control. Tumor cells were implanted into nude mice for in vivo analysis. Cerulenin was used as a FASN inhibitor. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect expression levels of FASN and ErbB1-4...
November 2017: Oncology Letters
Katharina Stoiber, Olga Nagło, Carla Pernpeintner, Siwei Zhang, Andreas Koeberle, Melanie Ulrich, Oliver Werz, Rolf Müller, Stefan Zahler, Theobald Lohmüller, Jochen Feldmann, Simone Braig
BACKGROUND: Although altered membrane physiology has been discussed within the context of cancer, targeting membrane characteristics by drugs being an attractive therapeutic strategy has received little attention so far. METHODS: Various acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN) inhibitors (like Soraphen A and Cerulenin) as well as genetic knockdown approaches were employed to study the effects of disturbed phospholipid composition on membrane properties and its functional impact on cancer progression...
November 7, 2017: British Journal of Cancer
Xiaoyu Liao, Lingyu Song, Linlin Zhang, Hui Wang, Qiang Tong, Jing Xu, Gangyi Yang, Shiming Yang, Hongting Zheng
Lysosome associated membrane protein 3 (LAMP3), a highly glycosylated protein, is one member of the LAMPs family. LAMPs family plays a critical role in the autolysosome fusion process. Autophagy was recently confirmed to regulate hepatic lipolysis. However, the physiological function of LAMP3 in lipid metabolism is not clear. In the current study, we discovered that the LAMP3 expression level was higher in the liver tissues of non-alcoholic fatty liver disease (NAFLD) patients and high-fat diet and ob/ob mice than in the matched control groups...
October 19, 2017: Molecular and Cellular Endocrinology
Fen-Fen Chen, Yan Xiong, Ying Peng, Yun Gao, Jin Qin, Gui-Yan Chu, Wei-Jun Pang, Gong-She Yang
Intramuscular fat (IMF) content affects the tenderness, juiciness, and flavor of pork. An increasing number of studies are focusing on the functions of microRNAs (miRs) during porcine intramuscular preadipocyte development. Previous studies have proved that miR-425-5p was enriched in porcine skeletal muscles and played important roles in multiple physiological processes; however, its functions during intramuscular adipogenesis remain unclear. To explore the role of miR-425-5p in porcine intramuscular adipogenesis, miR-425-5p agomir and inhibitor were used to perform miR-425-5p overexpression and knockdown in intramuscular preadipocytes, respectively...
October 6, 2017: International Journal of Molecular Sciences
Manjusha M Kulkarni, Annette N Ratcliff, Menakshi Bhat, Yazan Alwarawrah, Philip Hughes, Jesus Arcos, David Loiselle, Jordi B Torrelles, Nicholas T Funderburg, Timothy A Haystead, Jesse J Kwiek
BACKGROUND: Like all viruses, HIV-1 relies on host systems to replicate. The human purinome consists of approximately two thousand proteins that bind and use purines such as ATP, NADH, and NADPH. By virtue of their purine binding pockets, purinome proteins are highly druggable, and many existing drugs target purine-using enzymes. Leveraging a protein affinity media that uses the purine-binding pocket to capture the entire purinome, we sought to define purine-binding proteins regulated by HIV-1 infection...
September 29, 2017: Retrovirology
Javier A Menendez, Ruth Lupu
Ten years ago, we put forward the metabolo-oncogenic nature of fatty acid synthase (FASN) in breast cancer. Since the conception of this hypothesis, which provided a model to explain how FASN is intertwined with various signaling networks to cell-autonomously regulate breast cancer initiation and progression, FASN has received considerable attention as a therapeutic target. However, despite the ever-growing evidence demonstrating the involvement of FASN as part of the cancer-associated metabolic reprogramming, translation of the basic science-discovery aspects of FASN blockade to the clinical arena remains a challenge...
November 2017: Expert Opinion on Therapeutic Targets
J Z Walz, J Saha, A Arora, A Khammanivong, M G O'Sullivan, E B Dickerson
Oral squamous cell carcinoma (OSCC) is an aggressive and treatment-resistant malignancy in both feline and human patients. Recent work has demonstrated aberrant expression of fatty acid synthase (FASN) and an increased capacity for lipogenesis in human OSCC and other cancers. In human OSCC, inhibition of FASN decreased cell viability and growth in vitro, and diminished tumour growth and metastasis in murine preclinical models. This study aimed to characterize FASN as a therapeutic target in feline OSCC. Immunohistochemistry revealed high FASN expression in primary feline OSCC tumours, and FASN expression was detected in OSCC cell lines (3 feline and 3 human) by immunoblotting and quantitative real-time-polymerase chain reaction (qRT-PCR)...
March 2018: Veterinary and Comparative Oncology
Meiqiang Chu, Yong Zhao, Shuai Yu, Yanan Hao, Pengfei Zhang, Yanni Feng, Hongfu Zhang, Dongxue Ma, Jing Liu, Ming Cheng, Lan Li, Wei Shen, Hongfang Cao, Qiang Li, Lingjiang Min
Mammary epithelial cells are regulated by steroid hormones, growth factors, and even microRNAs. MiR-15b has been found to regulate lipid metabolism in adipocytes; however its effects on lipid metabolism in mammary epithelial cells, the cells of lipid synthesis and secretion, are as yet unknown. The main purpose of this investigation was to explore the effect of miR-15b on lipid metabolism in mammary epithelial cells, along with the underlying mechanisms. MiR-15b was overexpressed or inhibited by miRNA mimics or inhibitors; subsequently lipid formation in mammary epithelial cells, and proteins related to lipid metabolism, were investigated...
August 23, 2017: American Journal of Physiology. Cell Physiology
Fahim Ahmad, Shruti Patrick, Touseef Sheikh, Vikas Sharma, Pankaj Pathak, Prit Benny Malgulwar, Anupam Kumar, Shanker Datt Joshi, Chitra Sarkar, Ellora Sen
Elevated expression of enhancer of zeste homolog 2 (EZH2) - a histone H3K27 methyltransferase was observed in gliomas harboring telomerase reverse transcriptase (TERT) promoter mutations. Given the known involvement of TERT and EZH2 in glioma progression, the co-relation between the two and subsequently its involvement in metabolic programming was investigated. Inhibition of hTERT either pharmacologically or through genetic manipulation not only decreased EZH2 expression, but also (i) abrogated FASN levels, (ii) decreased de novo fatty acid accumulation, and (iii) increased Ataxia-telangiectasia mutated (ATM) phosphorylation levels...
August 21, 2017: Journal of Neurochemistry
Saber Tadros, Surendra K Shukla, Ryan J King, Venugopal Gunda, Enza Vernucci, Jaime Abrego, Nina V Chaika, Fang Yu, Audrey J Lazenby, Lyudmyla Berim, Jean Grem, Aaron R Sasson, Pankaj K Singh
Pancreatic adenocarcinoma is moderately responsive to gemcitabine-based chemotherapy, the most widely used single-agent therapy for pancreatic cancer. Although the prognosis in pancreatic cancer remains grim in part due to poor response to therapy, previous attempts at identifying and targeting the resistance mechanisms have not been very successful. By leveraging The Cancer Genome Atlas dataset, we identified lipid metabolism as the metabolic pathway that most significantly correlated with poor gemcitabine response in pancreatic cancer patients...
October 15, 2017: Cancer Research
Wendi Sun, Hiroyuki Kato, Shojiro Kitajima, Kian Leong Lee, Katarina Gradin, Takashi Okamoto, Lorenz Poelllinger
Hypoxia-inducible factors (HIFs) play a central role in the transcriptional response to changes in oxygen availability. Stability of HIFs is regulated by multi-step reactions including recognition by the von Hippel-Lindau tumour suppressor protein (pVHL) in association with an E3 ligase complex. Here we show that pVHL physically interacts with fatty acid synthase (FASN), displacing the E3 ubiquitin ligase complex. This results in HIF-α protein stabilization and activation of HIF target genes even in normoxia such as during adipocyte differentiation...
August 3, 2017: Scientific Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"