Blockade of long chain fatty acid oxidation by non-steroidal anti-inflammatory drugs may contribute to inhibition of proliferation of human colorectal carcinoma cell lines.
Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the growth of colorectal carcinoma (CRC) cell lines. Although the mechanism appears to be independent of cyclooxygenases, the inhibitory target has not previously been defined. We now report for the first time that NSAIDs inhibit oxidation of the long chain fatty acid palmitate in human CRC cell lines with potencies which are in good agreement with the potencies of NSAIDs as inhibitors of cell proliferation. The absence of inhibition of acetate oxidation rules out an effect on mitochondrial functions. We conclude that the long chain fatty acid oxidation pathway may be a novel target for some of the inhibitory effects of NSAIDs on the growth of CRC cell lines.
Yang
Z
Z
University Department of Surgery, Melbourne, Victoria, Australia.
Hollande
F
F
Baldwin
G S
GS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D005227:Fatty Acids