Influence of free fatty acids on glucose uptake in prostate cancer cells

Abstract

Introduction The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate. Methods Human prostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco’s Modified Eagle’s Medium (DMEM) with varying concentrations of the free fatty acid palmitate (0–1.0 mM). Then the cells were incubated with [18 F]-FDG (1 µCi/mL; 0.037 MBq/mL) in DMEM either in presence or absence of glucose and in presence of varying concentrations of palmitate for 1 h. Standardized procedures regarding cell counting and measuring for 18F radioactivity were applied. Cell uptake studies with 14C-1-acetate under the same conditions were performed on PC3 cells. Results In glucose containing media there was significantly increased FDG uptake after 24 h incubation in all cell lines, except DU145, when upper physiological levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells (15.11% vs. 3.94%/106 cells) was observed in media with 1.0 mM palmitate compared to media with no palmitate. The same tendency was observed in PC3 and CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant differences in FDG uptake after 24 h incubation were observed. The significant differences after 2 h incubation all pointed in the direction of increased FDG uptake when palmitate was added. Acetate uptake in PC3 cells was significantly lower when palmitate was added in glucose-free DMEM. No clear tendency when comparing FDG or acetate uptake in the same media at different time points of incubation was observed. Conclusions Our results indicate a FFA dependent metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the true heterogeneity of the disease.

On the Origin of ATP Synthesis in Cancer

“…The palmitate-induced increase in oxygen consumption, glycolysis, and neutral lipid storage was greater in mitochondria from MDA-231 triple-negative breast cancer cells than from normal cells (Park et al, 2016). Andersen et al also showed that palmitic acid could enhance glucose uptake in several prostate cancer cell lines suggesting that fatty acids enhance glycolysis through the PI3K/Akt pathway (Andersen et al, 2014). ATP synthesis from fatty acid oxidation occurs only if OxPhos is intact, which is not the case for the majority of cancers.…”

<p>Free Fatty Acids Promote the Development of Prostate Cancer by Upregulating Peroxisome Proliferator-Activated Receptor Gamma</p>

“…10 Therefore, in our present study, we first analyzed and compared the changes in the fatty acid difference spectrum in serum of patients with PCa, combined with the existing literature, OA/PA = 2/1 was used to simulate the PC3 and 22RV1 cells. 11,[34][35][36] The results showed that a high concentration of FFA can significantly enhance the ability of proliferation, migration, and invasion of PCa cells. The above results suggest that the increase of serum OA and PA may be an important risk factor for the development of obesityrelated PCa.…”

“…9,10 Existing literature has suggested that in the presence of palmitate, the glucose metabolism levels of PCa cells PC3 and CWR22RV1 are significantly increased. 11 Other literature has suggested that OA promotes an aggressive phenotype in PCa cells via FFA1/GPR40, calcium and PI3K/Akt signaling. 12 In addition, fatty acids can also act as specific receptors that affect intracellular signaling, thereby regulating castration resistance and metastasis of PCa.…”

Mitochondrial oncobioenergetics of prostate tumorigenesis (Review)

“…However, glucose seems to be the preferred substrate. Studies have shown that PECs consume high amounts of glucose (13–15) and have higher aerobic glycolysis (10) compared to other cell types (11,16), such as normal breast epithelial cells or cells with rapid cell turnover such as monocytes (17). Acetyl CoA is mainly generated from pyruvate and β-oxidation of fatty acids.…”