Down-regulation Of Fatty Acid Synthase Expression Research Articles

Fatty acid synthase, a novel poor prognostic factor for acute lymphoblastic leukemia which can be targeted by ginger extract

Altered metabolism of fatty acid synthesis is considered a hallmark characteristic of several malignancies, including acute lymphoblastic leukemia (ALL). To evaluate the impact of fatty acid synthase (FASN) on drug resistant ALL, bone marrow samples were collected from 65 pediatric ALLs, including 40 de novo and 25 relapsed patients. 22 non-cancer individuals were chosen as controls. Quantitative RT-PCR showed increased expression levels of FASN in drug resistant patients compared with the therapy responders. Single and combined treatment of malignant cells were analyzed using Annexin-V/PI double staining and MTT assays. Incubation of resistant primary cells with ginger showed simultaneous increased apoptosis rates and reduced FASN expression levels. Furthermore, docking studies demonstrated high affinity bindings between ginger derivatives and FASN thioesterase and ketosynthase domains, compared with their known inhibitors, fenofibrate and morin, respectively. Finally, combined treatment of in-house multidrug resistant T-ALL subline with ginger and dexamethasone induced drug sensitivity and down regulation of FASN expression, accordingly. To the best of our knowledge, this is the first study that introduces FASN upregulation as a poor prognostic factor for drug resistant childhood ALL. Moreover, it was revealed that FASN inhibition may be applied by ginger phytochemicals and overcome dexamethasone resistance, subsequently.

Effect of down-regulation of fatty acid synthase expression on proliferation, migration and invasion of bladder carcinoma UMUC3 cell lines

To investigate the effects of fatty acid synthase (FASN) on proliferation, migration and invasion of bladder cancer UMUC3 cell lines and possible mechanism. The expression levels of FASN protein in 30 cases of bladder cancer and 15 cases of normal bladder tissues were detected by Immunohistochemistry. FASN siRNA and nonsense siRNA were transfected into UMUC3 cell lines by lipofectamine 2000 respectively, and the stable siFASN and siControl cell lines were successfully obtained after screening and identification for several times. The siFASN cell lines were set as the experimental group, while the siControl cell lines were set as the control group. The expressions of FASN protein and mRNA in the experimental group and the control group were detected by Western blot and real-time quantitative PCR (RT-PCR) respectively. Cell proliferation activities in two groups were detected by MTT assay and cell invasion and migration in two groups were detected by cell scratch test and Transwell invasive assays respectively. FASN protein was overexpressed in bladder cancer tissues, and it was closely correlated with pathological stage and grade (P＜0.05). Compared with the siControl group, the expressions of FASN mRNA and protein in the siFASN group cell lines were decreased significantly (P＜0.05). The cell proliferation ability, the migration ability and the number of transmembrane cells of siFASN group cell lines were reduced significantly (P＜0.05). The FASN overexpression may play an essential role in the development and progression of bladder cancer. Down-regulation of FASN expression can inhibit the proliferation, migration and invasion of bladder cancer cells, and inhibition of FASN expression is expected to be a new treatment for bladder cancer.

Inhibition Effect of Triglyceride Accumulation by Large Yellow Croaker Roe DHA-PC in HepG2 Cells.

The phospholipids (PLs) of large yellow croaker (Pseudosciaena crocea, P. crocea) roe contain a high level of polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), which can lower blood lipid levels. In previous research, PLs of P. crocea roe were found able to regulate the accumulation of triglycerides. However, none of these involve the function of DHA-containing phosphatidylcholine (DHA-PC), which is the main component of PLs derived from P. crocea roe. The function by which DHA-PC from P. crocea roe exerts its effects has not yet been clarified. Herein, we used purified DHA-PC and oleic acid (OA) induced HepG2 cells to establish a high-fat model, and the cell activity and intracellular lipid levels were then measured. The mRNA and protein expression of Fatty Acid Synthase (FAS), Carnitine Palmitoyl Transferase 1A (CPT1A) and Peroxisome Proliferator-Activated Receptor α (PPARα) in HepG2 cells were detected via RT-qPCR and western blot as well. It was found that DHA-PC can significantly regulate triglyceride accumulation in HepG2 cells, the effect of which was related to the activation of PPARα receptor activity, upregulation of CPT1A, and downregulation of FAS expression. These results can improve the understanding of the biofunction of hyperlipidemia mediated by DHA-PC from P. crocea roe, as well as provide a theoretical basis for the utilization of DHA-PC from P. crocea roe as a functional food additive.

Fatty Acid Synthase and AKT Pathway Signaling in a Subset of Papillary Thyroid Cancers

Fatty acid synthase (FASN) is an enzyme that plays a critical role in de novo synthesis of fatty acids. FASN is overexpressed in variety of human cancers, but its role has not been elucidated in papillary thyroid carcinoma (PTC). Our objective was to investigate the role of FASN and its relationship with phosphatidylinositol 3-kinase/AKT activation in a large series of PTC in a tissue microarray format followed by studies using PTC cell lines and Nude mice. Analysis of apoptosis and cell cycle were evaluated by flow cytometry and DNA fragmentation assays. FASN and phospho-AKT protein expression was determined by immunohistochemistry and Western blotting. Our data show that expression of FASN is associated with activated AKT (phospho-AKT) in a subset of PTC. Treatment of PTC cell lines (NPA-187, ONCO-DG-1, and B-CPAP) with C-75, an inhibitor of FASN, suppresses growth and induces apoptosis in all cell lines. Treatment of PTC cells with C-75 or expression of FASN small interfering RNA causes down-regulation of FASN and inactivation of AKT activity. Furthermore, treatment of PTC cell lines with C-75 results in apoptosis via the mitochondrial pathway involving the proapoptotic factor Bad, activation of Bax, activation of caspases, and down-regulation of antiapoptotic proteins. Finally, treatment of NPA-187 xenografts with C-75 results in growth inhibition of tumors in Nude mice via down-regulation of FASN expression and inactivation of AKT. Our results suggest that FASN and activated AKT pathway may be a potential target for therapeutic intervention for the treatment of PTC.