Pharmacological Inhibitor of Fatty Acid Synthase Suppresses Growth and Invasiveness of Renal Cancer Cells

Purpose: Fatty acid synthase has been shown to be over expressed in a wide range of cancers and it has emerged as a therapeutic target. We examined whether fatty acid synthase could be a novel therapeutic target for renal cell carcinoma using the pharmacological fatty acid synthase inhibitor C75 (Cayman Chemical, Ann Arbor, Michigan). Materials and Methods: The effects of C75 on cell viability and proliferation in human renal cancer 769P (ATCC®), Caki-1 and KU20-01 cells were examined by MTS assay and cell counts. Cell cycle distribution was analyzed by flow cytometry and cell invasiveness was assessed by wound healing and Matrigel^™ invasion assays. Fatty acid synthase expression and the effects of C75 on intracellular signaling pathways were analyzed by Western blotting. The antitumor efficacy of C75 was examined using Caki-1 cell xenografts. Results: All renal cancer cell lines expressed detectable fatty acid synthase. C75 (10 μg/ml) significantly inhibited cell viability and growth by arresting the cell cycle at the G2/M phase and inducing apoptosis (p <0.01). The covered area in the wound and the number of cells invading through a Matrigel chamber were significantly smaller for cells treated with C75 than they were for control cells treated with vehicle (p <0.001). C75 suppressed Her2 and epidermal growth factor receptor expression as well as STAT3 phosphorylation, while increasing p53 and p21^Waf1/Cip1 expression. Intraperitoneal administration of C75 at doses of 20 mg/kg per week for 28 days significantly reduced the tumor volume of Caki-1 xenografts (p <0.05). Conclusions: Pharmacological inhibition of fatty acid synthase could be an effective strategy for treating renal cell carcinoma.