Profiling lipoxygenase metabolism in specific steps of colorectal tumorigenesis.
Lipoxygenases (LOX) are key enzymes for the oxidative metabolism of polyunsaturated fatty acids into biologically active products. Clinical data on comparative levels of various LOX products in tumorigenesis are lacking. Therefore, we examined the profiles of several LOX products (5-LOX, 12-LOX, 15-LOX-1, and 15-LOX-2) by liquid chromatography/tandem mass spectrometry in the major steps of colorectal tumorigenesis (normal, polyp, and cancer) in a clinical study of 125 subjects (49 with normal colon, 36 with colorectal polyps, and 40 with colorectal cancer) who underwent prospective colorectal biopsies to control for various potential confounding factors (e.g., diet, medications). Mean 13-hydroxyoctadecadienoic acid (13-HODE) levels were significantly higher in normal colon [mean, 36.11 ng/mg protein; 95% confidence interval (95% CI), 31.56-40.67] than in paired colorectal cancer mucosa (mean, 27.01 ng/mg protein; 95% CI, 22.00-32.02; P = 0.0002), and in normal colon (mean, 37.15 ng/mg protein; 95% CI, 31.95-42.34) than in paired colorectal polyp mucosa (mean, 28.07 ng/mg protein; 95% CI, 23.66-32.48; P < 0.001). Mean 13-HODE levels, however, were similar between the left (mean, 37.15 ng/mg protein; 95% CI, 31.95-42.35) and the right normal colon (mean, 32.46 ng/mg protein; 95% CI, 27.95-36.98; P = 0.09). No significant differences with regard to 12- or 15-hydroxyeicosatetraenoic acid or leukotriene B(4) levels were detected between normal, polyp, and cancer mucosae. 15-LOX-1 inhibited interleukin-1beta expression. This study establishes that reduced 13-HODE levels are a specific alteration in the LOX product profile associated with human colorectal tumorigenesis.
Shureiqi
Imad
I
Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, 77030-4009, USA. ishureiqi@mdandesron.org
Chen
Dongning
D
Day
R Sue
RS
Zuo
Xiangsheng
X
Hochman
Fredric Lyone
FL
Ross
William A
WA
Cole
Rhonda A
RA
Moy
Ofie
O
Morris
Jeffrey S
JS
Xiao
Lianchun
L
Newman
Robert A
RA
Yang
Peiying
P
Lippman
Scott M
SM
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D053583:Interleukin-1beta; D008041:Linoleic Acids; C024348:13-hydroxy-9,11-octadecadienoic acid; D008084:Lipoxygenase