Abstract 1300: Fatty acid synthase (FASN) inhibition negatively affects cell proliferation and the metastatic capability of prostate cancer cells

Abstract

Abstract Purpose Fatty acid synthase (FASN) is a key metabolic enzyme that catalyzes the synthesis of fatty acids (FA). Recent data has shown that several common cancers express elevated levels of fatty acid synthase (FASN) in comparison to normal tissue; with prostate cancer being one. This information has implicated FASN as a possible oncogene and marker for cancer malignancy involving invasion and migration. Three of the most common prostate cancer cell lines (DU145, PC3, and LNCaP) all express elevated FASN levels with LNCaP cells exhibiting the highest levels of FASN among the three cell lines. This study aimed to investigate the effects of a novel FASN inhibitor (1B) designed in our lab on three different prostate cancer cell lines and compare its cytotoxic and phenotypic effects on cell proliferation and viability, apoptosis, lipid levels, and expression and regulation of key cellular proteins involved in FA synthesis to the well-known FASN inhibitor Orlistat and FASN siRNA. Experimental Methods DU145, PC3, and LNCaP prostate cancer cell lines were used in all experiments. Cells were exposed to Orlistat and 1B doses of 50 and 100μM for 24h and 48h time points. Cell viability was assessed using the MTT assay, and cell proliferation was assessed using the CyQUANT cell proliferation kit. Western blotting was used to analyz e the relevant protein expression with the immune complexes detected by chemiluminescence. Apoptosis analysis by microscopy was done using the Hoechst dye stain. The percentage of cells having stained nuclei indicating apoptosis was scored by fluorescence microscopy. Results Cell proliferation and viability data indicates a dose-dependent decrease in all three cell lines for both Orlistat and 1B. Apoptosis analysis also revealed an increase in cell death in all three cell lines when treated with either drug. Most interestingly, there was a more significant decrease in cell viability and proliferation in LNCaP cells in comparison to DU145 and PC3 cells; an expected result considering that LNCaP cells express higher levels of FASN. Similar data was also seen when utilizing siRNA to FASN. Conclusions We conclude that FASN inhibition (by both drug treatment and siRNA) negatively affects cellular viability, proliferation, and apoptosis. Further experimental analysis will determine whether this inhibition also negatively affects cell cycle progression, related protein expression levels, and the ability of these prostatic cells to undergo invasion and migration; a hallmark of prostate cancer progression. Citation Format: Clayton Wright, Anand Krishnan V. Iyer, Neelam Azad. Fatty acid synthase (FASN) inhibition negatively affects cell proliferation and the metastatic capability of prostate cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1300.