Decreased Cellular Levels of Palmitic Amide are Linked to 5-fluorouracil Resistance in Human Colon Cancer Cells

Abstract

Background/Aims: The aim of this study was to investigate whether profiling metabolic compounds in human colon cancer cells with induced 5-florouracil resistance enables identification of predictive bio-markers for 5-florouracil resistance. Methodology: 5-florouracil resistant and parental cells were extracted using methanol/chloroform solution, and analyzed by MALDI-TOF. Principal components analysis and discriminant analysis was performed to select low-mass ions with strong discriminating power between 5-florouracil resistant and parental cells. The correlation between the intensities of low-mass ions and intrinsic 5-florouracil resistance in 11 colon cancer cells was analyzed using the Spearman rank coefficient. Results: Eleven low-mass ions had strong discriminating power between 5-florouracil-resistant and parental cells. Of these, the intensity of a low-mass ion with 256.29m/z was negatively correlated with intrinsic 5-florouracil resistance in 11 colon cancer cells (r = -0.6545, P = 0.0338). By searching the H+ adduct with 0.05 m/z tolerance in the Human Metabolome Database, a low-mass ion of 256.29 m/z was identified as palmitic amide. Interestingly, extracellular treatment with palmitic amide reduced 5-florouracil resistance and invasiveness in 5-florouracil-resistant cells. Conclusions: Palmitic amide showed potential not only as a predictor of 5-florouracil resistance, but also for reduction of 5-florouracil resistance in colon cancer cells.