Lipidomics Profiling Reveals Differential Alterations after FAS Inhibition in 3D Colon Cancer Cell Culture Models

• DOI: 10.1021/acs.jproteome.3c00593
• Publication Date: 2023-12-08T13:14:46Z
• Authors: Brian D. Fries; Fernando Tobias; Yijia Wang; Joseph H. Holbrook; Amanda B. Hummon
• Keywords: Cerulenin; Lipidome; Lipogenesis

Cancerous cells synthesize most of their lipids de novo to keep up with rapid growth and proliferation. Fatty acid synthase (FAS) is a key enzyme in the lipogenesis pathway that upregulated many cancers has gained popularity as druggable target interest for cancer treatment. The first FAS inhibitor discovered, cerulenin, initially showed promise chemotherapeutic purposes until it was observed had adverse side effects mice. TVB-2640 (Denifanstat) part newer generation inhibitors. With multiple generations inhibitors being developed, vital understand distinct molecular downstream elucidate potential interactions clinic. Here, we profile lipidome two different colorectal (CRC) spheroids treated 1 (cerulenin) or 2 (TVB-2640). We observe cerulenin causes drastic changes spheroid morphology well alterations lipid droplets found within CRC spheroids. higher abundances polyunsaturated fatty acids (PUFAs) whereas decreased abundance PUFAs. increase PUFAs exposed indicates causing die via ferroptotic mechanism rather than conventional apoptotic necrotic mechanism.