fatty acid binding prostate cancer

Sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor in lipogenesis and lipid metabolism, is critical for disease progression and associated with poor outcomes in prostate cancer (PCa) patients. However, the mechanism of SREBP-1 regulation in PCa remains elusive. Here, we report that SREBP-1 is transcriptionally regulated by microRNA-21 (miR-21) in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of SREBP-1, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC) in Pten/Trp53 double-null mouse embryonic fibroblasts (MEFs) and Pten/Trp53 double-null mutant mice...

Lipocalin-2 (LCN-2) is a novel, 198 amino acid adipocytokine also referred to as neutrophil gelatinase-associated lipocalin (NGAL). LCN-2 is a circulatory protein responsible for the transportation of small and hydrophobic molecules (steroid, free fatty acids, prostaglandins and hormones) to target organs after binding to megalin/glycoprotein and GP330 SLC22A17 or 24p3R LCN-2 receptors. LCN-2 has been used as a biomarker for acute and chronic renal injury. It is present in a large variety of cells including neutrophil, hepatocytes, lung, bone marrow, adipose tissue, macrophages, thymus, non-neoplastic breast duct, prostate, and renal cells...

BACKGROUND: Caveolae proteins play diverse roles in cancer development and progression. In prostate cancer, non-caveolar caveolin-1 (CAV1) promotes metastasis, while CAVIN1 attenuates CAV1-induced metastasis. Here, we unveil a novel mechanism linking CAV1 to selective loading of exosomes with metastasis-promoting microRNAs. RESULTS: We identify hnRNPK as a CAV1-regulated microRNA binding protein. In the absence of CAVIN1, non-caveolar CAV1 drives localisation of hnRPNK to multi-vesicular bodies (MVBs), recruiting AsUGnA motif-containing miRNAs and causing their release within exosomes...

PURPOSE: 5' adenosine monophosphate-activated kinase (AMPK) is an essential regulator of cellular energy homeostasis and has been associated with different pathologies, including cancer. Precisely defining the biological role of AMPK necessitates the availability of a potent and selective inhibitor. METHODS: High-throughput screening and chemical optimization were performed to identify a novel AMPK inhibitor. Cell proliferation and mechanistic assays, as well as gene expression analysis and chromatin immunoprecipitation were used to investigate the cellular impact as well as the crosstalk between lipid metabolism and androgen signaling in prostate cancer models...

Lipid metabolism reprogramming is now accepted as a new hallmark of cancer. Hence, targeting the lipogenesis pathway may be a potential avenue for cancer treatment. Valproic acid (VPA) emerges as a promising drug for cancer therapy; however, the underlying mechanisms are not yet fully understood. In this study, we aimed to investigate the effects and mechanisms of VPA on cell viability, lipogenesis, and apoptosis in human prostate cancer PC-3 and LNCaP cells. The results showed that VPA significantly reduced lipid accumulation and induced apoptosis of PC-3 and LNCaP cells...

Treatment for early stage and localized prostate cancer (PCa) is highly effective. Patient survival, however, drops dramatically upon metastasis due to drug resistance and cancer recurrence. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. It is therefore crucial to decipher the key genetic alterations and relevant molecular pathways driving PCa metastatic progression so that predictive biomarkers and precise therapeutic targets can be developed. Through PCa cohort analysis, we found that a fatty acid-binding protein (FABP) gene cluster (containing five FABP family members) is preferentially amplified and overexpressed in metastatic PCa...

Ferroptosis, a form of regulated necrosis driven by iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various signaling pathways related to cancer. In this study, we found that activating mutation of phosphatidylinositol 3-kinase (PI3K) or loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) function, highly frequent events in human cancer, confers ferroptosis resistance in cancer cells, and that inhibition of the PI3K-AKT-mTOR signaling axis sensitizes cancer cells to ferroptosis induction...

Androgen deprivation therapy has led to elevated cases of androgen receptor (AR) pathway-independent prostate cancer with dysregulated fatty acid metabolism. However, it is unclear how prostate cancer cells sustain dysregulated fatty acid metabolism to drive AR-independent prostate cancer. Long-chain acyl-CoA synthetases (ACSL) catalyze the conversion of fatty acids into fatty acyl-CoAs that are required for fatty acid metabolism. In this study, we demonstrate that expression levels of ACSL3 and 4 were oppositely regulated by androgen-AR signaling in prostate cancer cells...

Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid-binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial-to-mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid β-oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production...

Emerging evidence suggests that dysregulated lipid signaling is a key factor in prostate cancer (PC), through fatty acid activation of the nuclear receptors peroxisome proliferator-activated receptors (PPARs), leading to the upregulation of protumoral genes. Fatty acid-binding proteins (FABPs) are intracellular lipid-binding proteins that transport fatty acid to PPARs, facilitating their activation. FABP5 is overexpressed in PC, and correlates with poor patient prognosis and survival. Genetic knockdown or silencing of FABP5 decreases the proliferation and invasiveness of PC cells in vitro, and reduces tumor growth and metastasis in vivo...

Peroxisome proliferator-activated receptor (PPAR), a ligand dependant transcription factor, is a member of the nuclear receptor superfamily. PPAR exists in three isoforms i.e. PPAR alpha (PPARα), PPAR beta (PPARβ), and PPAR gamma (PPARγ). These are multi-functional transcription factors and help in regulating inflammation, type 2 diabetes, lipid concentration in the body, metastasis, and tumor growth or angiogenesis. Activation of PPARγ causes inhibition of growth of cultured human breast, gastric, lung, prostate, and other cancer cells...

BACKGROUND: Prostate cancer is characterized by aberrant lipid metabolism, including elevated fatty acid oxidation. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of fatty acid oxidation. This study aimed to determine if CPT1B has a critical role in prostate cancer progression and to identify its regulatory mechanism. METHODS: CPT1B expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases was compared with patient survival data...

BACKGROUND: Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods : LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion...

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...

OBJECTIVES: To investigate the role of serum fatty acid-binding protein-4 (FABP-4) as a surrogate of obesity and metabolic syndrome in the prediction of the outcome of prostate biopsy. METHODS: A prospective pilot study was conducted for patients undergoing prostate needle biopsy (PNB) for clinically suspected prostate cancer (PCa) between June 2016 and August 2017. Fifty consecutive patients with biopsy-proven PCa were included as study group and 50 consecutive patients with negative biopsy were included as a control group...

Curcumin has a protective role in placental diseases like preeclampsia and preterm birth. Very little is known about its functional effects on growth, angiogenesis and epigenetic activities of human first trimester placenta. HTR8/SVneo trophoblasts cells were used as model for human first trimester placenta. Effects of curcumin (≥80%) in these cells were investigated using MTT, radioactive thymidine uptake, qRT-PCR, Promoter DNA methylation, qRT-PCR array, tube formation, wound healing and immunoblot assays...

Prostate cancer (PCa) is defined by dysregulated lipid signaling and is characterized by upregulation of lipid metabolism-related genes including fatty acid binding protein 5 (FABP5), fatty acid synthase (FASN), and monoacylglycerol lipase (MAGL). FASN and MAGL are enzymes that generate cellular fatty acid pools while FABP5 is an intracellular chaperone that delivers fatty acids to nuclear receptors to enhance PCa metastasis. Since FABP5, FASN, and MAGL have been independently implicated in PCa progression, we hypothesized that FABP5 represents a central mechanism linking cytosolic lipid metabolism to pro-metastatic nuclear receptor signaling...

The aim of the present study was to characterize and evaluate the anti-cancer activity of proanthocyanidin-enriched fractions from adzuki beans. For this purpose, we concentrated proanthocyanidins from adzuki beans ( Vigna angularis ) into five fractions using Amberlite XAD-1180N, Toyopearl HW40F, and Sepacore C-18 reverse-phase flash column chromatography. Proanthocyanidin-enriched fractions were characterized as (epi)catechin hexamer, heptamer, and octamer, epigallocatechin-(epi)catechin pentamer, and epigallocatechin-(epi)catechin hexamer using electrospray ionization time-of-flight mass spectrometry and thiolytic degradation...

BACKGROUND: Prostate cancer (PCa) remains the second leading cause of cancer-related death among men. Taxanes, such as docetaxel and cabazitaxel are utilized in standard treatment regimens for chemotherapy naïve castration-resistant PCa. However, tumors often develop resistance to taxane chemotherapeutics, highlighting a need to identify additional therapeutic targets. Fatty acid-binding protein 5 (FABP5) is an intracellular lipid carrier whose expression is upregulated in metastatic PCa and increases cell growth, invasion, and tumor formation...

Increased de novo synthesis of fatty acids is implicated in the pathogenesis of human prostate cancer, but a safe and effective clinical inhibitor of this metabolic pathway is still lacking. We have shown previously that leelamine (LLM) suppresses transcriptional activity of androgen receptor, which is known to regulate fatty acid synthesis. Therefore, the present study was designed to investigate the effect of LLM on fatty acid synthesis. Exposure of 22Rv1, LNCaP, and PC-3 prostate cancer cells, but not RWPE-1 normal prostate epithelial cell line, to LLM resulted in a decrease in intracellular levels of neutral lipids or total free fatty acids...