Background: Fatty acids are classified as short-chain (SCFA), medium-chain (MCFA) or long-chain and hold promise as adjunctive chemotherapeutic agents for the treatment of colorectal cancer. The antineoplastic potential of MCFA remains underexplored; accordingly, we compared the MCFA lauric acid (C12:0) to the SCFA butyrate (C4:0) in terms of their capacity to induce apoptosis, modify glutathione (GSH) levels, generate reactive oxygen species (ROS), and modify phases of the cell cycle in Caco-2 and IEC-6 intestinal cell lines. Methods: Caco-2 and IEC-6 cells were treated with lauric acid, butyrate, or vehicle controls. Apoptosis, ROS, and cell cycle analysis were determined by flow cytometry. GSH availability was assessed by enzymology. Results: Lauric acid induced apoptosis in Caco-2 (p < 0.05) and IEC-6 cells (p < 0.05) compared to butyrate. In Caco-2 cells, lauric acid reduced GSH availability and generated ROS compared to butyrate (p < 0.05). Lauric acid reduced Caco-2 and IEC-6 cells in G0/G1 and arrested cells in the S and G2/M phases. Lauric acid induced apoptosis in IEC-6 cells compared to butyrate (p < 0.05). Butyrate protected IEC-6 cells from ROS-induced damage, whereas lauric acid induced high levels of ROS compared to butyrate. Conclusion: Compared to butyrate, lauric acid displayed preferential antineoplastic properties, including induction of apoptosis in a CRC cell line. (C) 2013 S. Karger AG, Basel