Fatty Acid Synthase Inhibitor Cerulenin Suppresses Colorectal Cancer in Combination with Oxaliplatin

Fatty acid synthase (FASN) is highly expressed in many kinds of human cancers, and the potential use of FASN inhibitors were reported. Colorectal cancer (CRC) is one of the most common cancers with over one million new cases per year. The main cause of death by CRC is distant metastasis, especially liver metastasis. The effective chemotherapy for CRC is required worldwide. Expression of FASN was evaluated in both murine and human CRC cell lines. Cerulenin, a natural inhibitor of FASN, induces apoptosis in these cell lines. The ability of cerulenin to prevent the development of liver metastases of CRC cell lines was investigated. The number and size of metastatic CRC in the liver are significantly reduced by treatment with cerulenin. Oxaliplatin is one of the best chemotherapeutic agents of CRC. Cerulenin has a synergistic effect with oxaliplatin in vitro and in vivo. Cerulenin treatment is associated with reduced levels of phosphorylated Akt in CRC cell lines, suggesting that inhibition of this signal transduction pathway might be involved in the chemopreventive activity of cerulenin. Based on this study, inhibiting FASN would be an effective strategy in treating liver metastases and unresectable CRC, especially in combination with oxaliplatin.