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Prostate cancer cells exhibit altered cellular metabolism but, notably, not the hallmarks of Warburg metabolism. Prostate cancer cells exhibit increased de novo synthesis of fatty acids (FA); however, little is known about how extracellular FAs, such as those in the circulation, may support prostate cancer progression. Here, we show that increasing FA availability increased intracellular triacylglycerol content in cultured patient-derived tumor explants, LNCaP and C4-2B spheroids, a range of prostate cancer cells (LNCaP, C4-2B, 22Rv1, PC-3), and prostate epithelial cells (PNT1). Extracellular FAs are the major source (∼83%) of carbons to the total lipid pool in all cell lines, compared with glucose (∼13%) and glutamine (∼4%), and FA oxidation rates are greater in prostate cancer cells compared with PNT1 cells, which preferentially partitioned extracellular FAs into triacylglycerols. Because of the higher rates of FA oxidation in C4-2B cells, cells remained viable when challenged by the addition of palmitate to culture media and inhibition of mitochondrial FA oxidation sensitized C4-2B cells to palmitate-induced apoptosis. Whereas in PC-3 cells, palmitate induced apoptosis, which was prevented by pretreatment of PC-3 cells with FAs, and this protective effect required DGAT-1-mediated triacylglycerol synthesis. These outcomes highlight for the first-time heterogeneity of lipid metabolism in prostate cancer cells and the potential influence that obesity-associated dyslipidemia or host circulating has on prostate cancer progression. IMPLICATIONS: Extracellular-derived FAs are primary building blocks for complex lipids and heterogeneity in FA metabolism exists in prostate cancer that can influence tumor cell behavior., (©2019 American Association for Cancer Research.)

It is known that oxytocin stimulates steroidogenesis in several organs by modulating activity of 3β-hydroxysteroid dehydrogenases (HSD3B) and steroid 5α-reductases (SRD5A). However, this has not been established in prostate cancer where these enzymes, key to local production of androgens, are increased. Analysis of both HSD3B and SRD5A activities using a live cell in situ colourimetric assay demonstrated that in PC-3 cells HSD3B activity was significantly increased by oxytocin whilst SRD5A activity was unchanged. This was confirmed in ELISA based assays of conversion of pregnenolone to progesterone and testosterone to dihydrotestosterone in cell lysates following treatment. In contrast, oxytocin significantly inhibited HSD3B activity in LNCaPs, but significantly increased activity of SRD5A, as confirmed by ELISA assays. Analysis of both cell lines by microarray and qRT-PCR determined that these changes were not due to altered gene transcription. This study demonstrates differential effects of oxytocin on the activities of key de novo steroidogenic enzymes in prostate cancer cells., (Copyright © 2015 Elsevier Inc. All rights reserved.)