Targeting fatty acid synthase with ASC-J9 suppresses proliferation and invasion of prostate cancer cells

2016 ◽  
Vol 55 (12) ◽  
pp. 2278-2290 ◽  
Author(s):  
Simeng Wen ◽  
Yuanjie Niu ◽  
Soo Ok Lee ◽  
Shuyuan Yeh ◽  
Zhiqun Shang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Prostate Cancer Cells ◽  
Proliferation And Invasion

Inhibition of fatty acid synthase activity in prostate cancer cells by dutasteride

The Prostate ◽  
2007 ◽  
Vol 67 (10) ◽  
pp. 1111-1120 ◽  
Author(s):  
Lucy J. Schmidt ◽  
Karla V. Ballman ◽  
Donald J. Tindall
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Prostate Cancer Cells

scholarly journals Citral Induced Apoptosis through Modulation of Key Genes Involved in Fatty Acid Biosynthesis in Human Prostate Cancer Cells: In Silico and In Vitro Study

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Sri Renukadevi Balusamy ◽  
Haribalan Perumalsamy ◽  
Karpagam Veerappan ◽  
Md. Amdadul Huq ◽  
S. Rajeshkumar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Human Prostate ◽  
Detection Methods ◽  
Potential Candidate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Apoptosis Pathway

The isomers of citral (cis-citral and trans-citral) were isolated from the Cymbopogon citratus (DC.) Stapf oil demonstrates many therapeutic properties including anticancer properties. However, the effects of citral on suppressing human prostate cancer and its underlying molecular mechanism have yet to be elucidated. The citral was isolated from lemongrass oil using various spectroscopic analyses, such as electron ionized mass spectrometry (EI-MS) and nuclear magnetic resonance (NMR) spectroscopy respectively. We carried out 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cell viability of citral in prostate cancer cells (PC-3 and PC3M). Furthermore, to confirm that PC3 undergoes apoptosis by inhibiting lipogenesis, we used several detection methods including flow cytometry, DNA fragmentation, Hoechst staining, PI staining, oil staining, qPCR, and Western blotting. Citral impaired the clonogenic property of the cancer cells and altered the morphology of cancer cells. Molecular interaction studies and the PASS biological program predicted that citral isomers tend to interact with proteins involved in lipogenesis and the apoptosis pathway. Furthermore, citral suppressed lipogenesis of prostate cancer cells through the activation of AMPK phosphorylation and downregulation of fatty acid synthase (FASN), acetyl coA carboxylase (ACC), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), and sterol regulatory element-binding protein (SREBP1) and apoptosis of PC3 cells by upregulating BAX and downregulating Bcl-2 expression. In addition, in silico studies such as ADMET predicted that citral can be used as a safe potent drug for the treatment of prostate cancer. Our results indicate that citral may serve as a potential candidate against human prostate cancer and warrants in vivo studies.

scholarly journals Deciphering Fatty Acid Synthase Inhibition-Triggered Metabolic Flexibility in Prostate Cancer Cells through Untargeted Metabolomics

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2447
Author(s):  
Ju Eun Oh ◽  
Byung Hwa Jung ◽  
Jinyoung Park ◽  
Soosung Kang ◽  
Hyunbeom Lee
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
De Novo Lipogenesis ◽  
Untargeted Metabolomics ◽  
Metabolic Phenotype ◽  
Polyamine Metabolism ◽  
Metabolic Flexibility ◽  
Prostate Cancer Cells

Fatty acid synthase (FAS) is a key enzyme involved in de novo lipogenesis that produces lipids that are necessary for cell growth and signal transduction, and it is known to be overexpressed, especially in cancer cells. Although lipid metabolism alteration is an important metabolic phenotype in cancer cells, the development of drugs targeting FAS to block lipid synthesis is hampered by the characteristics of cancer cells with metabolic flexibility leading to rapid adaptation and resistance. Therefore, to confirm the metabolic alterations at the cellular level during FAS inhibition, we treated LNCaP-LN3 prostate cancer cells with FAS inhibitors (Fasnall, GSK2194069, and TVB-3166). With untargeted metabolomics, we observed significant changes in a total of 56 metabolites in the drug-treated groups. Among the altered metabolites, 28 metabolites were significantly changed in all of the drug-treated groups. To our surprise, despite the inhibition of FAS, which is involved in palmitate production, the cells increase their fatty acids and glycerophospholipids contents endogenously. Also, some of the notable changes in the metabolic pathways include polyamine metabolism and energy metabolism. This is the first study to compare and elucidate the effect of FAS inhibition on cellular metabolic flexibility using three different FAS inhibitors through metabolomics. We believe that our results may provide key data for the development of future FAS-targeting drugs.

scholarly journals Inhibition of Fatty Acid Synthase Sensitizes Prostate Cancer Cells to Radiotherapy

2015 ◽  
Vol 184 (5) ◽  
pp. 482-493 ◽  
Author(s):  
Colin Rae ◽  
Uwe Haberkorn ◽  
John W. Babich ◽  
Robert J. Mairs
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Prostate Cancer Cells

KLF5 enhances SREBP-1 action in androgen-dependent induction of fatty acid synthase in prostate cancer cells

2008 ◽  
Vol 417 (1) ◽  
pp. 313-322 ◽  
Author(s):  
Min-Young Lee ◽  
Jong-Seok Moon ◽  
Sahng Wook Park ◽  
Yoo-kyung Koh ◽  
Yong-Ho Ahn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Mrna Level ◽  
Critical Role ◽  
Proximal Promoter ◽  
Prostate Cancer Cells ◽  
Atp Citrate Lyase

KLF5 (Krüppel-like factor 5) is a zinc-finger transcription factor that plays a critical role in the regulation of cellular signalling involved in cell proliferation, differentiation and oncogenesis. In the present study, we showed that KLF5 acts as a key regulator controlling the expression of FASN (fatty acid synthase) through an interaction with SREBP-1 (sterol-regulatory-element-binding protein-1) in the androgen-dependent LNCaP prostate cancer cell line. The mRNA level of KLF5 increased when cells were treated with a synthetic androgen, R1881. Furthermore, KLF5 bound to SREBP-1 and enhanced the SREBP-1-mediated increase in FASN promoter activity. The results also demonstrated that the expression of KLF5 in LNCaP prostate cancer cells enhanced FASN expression, whereas silencing of KLF5 by small interfering RNA down-regulated FASN expression. The proximal promoter region and the first intron of the FASN gene contain multiple CACCC elements that mediate the transcriptional regulation of the gene by KLF5. However, other lipogenic and cholesterogenic genes, such as those encoding acetyl-CoA carboxylase, ATP-citrate lyase, the LDL (low-density lipoprotein) receptor, HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) synthase and HMG-CoA reductase are irresponsive to KLF5 expression, owing to the absence of CACCC elements in their promoter regions. Taken together, these results suggest that the FASN gene is activated by the synergistic action of KLF5 and SREBP-1, which was induced by androgen in androgen-dependent prostate cancer cells.

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