Decreased cellular levels of palmitic amide are linked to 5-fluorouracil resistance in human colon cancer cells

• Published in: Hepato-gastroenterology Vol. 61; no. 130; p. 343
• Main Authors: Lee, Jun Hwa, Kim, Seung Cheol, Kim, Kyung-Hee, Kim, Won Ki, Lee, Min Jun, Yoo, Byong Chul, Yeo, Seung-Gu
• Format: Journal Article
• Language: English
• Published: Greece 01.03.2014
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biomarkers, Tumor - metabolism; Cell Line, Tumor; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Drug Resistance, Neoplasm; Drug Synergism; Fluorouracil - administration & dosage; Fluorouracil - pharmacology; Humans; Palmitic Acids - administration & dosage; Palmitic Acids - metabolism; Palmitic Acids - pharmacology; Principal Component Analysis; Signal Transduction - drug effects; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Statistics, Nonparametric
• ISSN: 0172-6390
• DOI: 10.5754/hge13979

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 biomarkers for 5-florouracil resistance. 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. Eleven low-mass ions had strong discrimi-nating power between 5-florouracil-resistant and parental cells. Of these, the intensity of a low-mass ion with 256.29 m/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. 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.