Overexpression of 5-lipoxygenase in sporadic colonic adenomas and a possible new aspect of colon carcinogenesis

Wasilewicz, Michał; Kołodziej, Blanka; Bojułko, Teresa; Kaczmarczyk, Mariusz; Sulżyc-Bielicka, Violetta; Bielicki, Dariusz; Ciepiela, Katarzyna

doi:10.1007/s00384-010-0980-z

Cited by 44 publications

(37 citation statements)

References 23 publications

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“…However, the tissue concentrations of 13S-HODE declined across this progressive sequence. In a separate study a strong correlation between ALOX5 expression and increased polyp size as well as higher tumor grade suggested a role for this enzyme in early stages of colon cancer [120]. These data are consistent with the overexpression of ALOX5 in colon polyps and carcinoma tissue described in another study [121].…”

Section: Biological Function Of Mammalian Lox Isoformssupporting

confidence: 85%

Mammalian lipoxygenases and their biological relevance

Kühn

Banthiya

Leyen

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

502

431

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Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders.

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Section: Biological Function Of Mammalian Lox Isoformssupporting

confidence: 85%

Mammalian lipoxygenases and their biological relevance

Kühn

Banthiya

Leyen

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

502

431

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“…The DHET metabolites were not significantly changed, but 12-HETEs did decrease. Products from 5- and 12-lipoxygenases have been associated with enhanced carcinogenesis in multiple epithelia (26, 27, 32). Colon 12-S- and 12-R-HETEs were substantially reduced by ω-3 fatty acid supplementation (Table 2).…”

Section: Discussionmentioning

confidence: 99%

The Anti-inflammatory Effect of Personalized Omega-3 Fatty Acid Dosing for Reducing Prostaglandin E2 in the Colonic Mucosa Is Attenuated in Obesity

Djurić

Turgeon

Sen

et al. 2017

Cancer Prevention Research

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This clinical trial developed a personalized dosing model for reducing prostaglandin E2 (PGE2) in colonic mucosa using ω-3 fatty acid supplementation. The model utilized serum eicosapentaenoic acid (EPA, ω-3):arachidonic acid (AA, ω-6) ratios as biomarkers of colonic mucosal PGE2 concentration. Normal human volunteers were given low and high ω-3 fatty acid test doses for 2 weeks. This established a slope and intercept of the line for dose versus serum EPA:AA ratio in each individual. The slope and intercept was utilized to calculate a personalized target dose that was given for 12 weeks. This target dose was calculated on the basis of a model, initially derived from lean rodents, showing a log-linear relationship between serum EPA:AA ratios and colonic mucosal PGE2 reduction. Bayesian methods allowed addition of human data to the rodent model as the trial progressed. The dosing model aimed to achieve a serum EPA:AA ratio that is associated with a 50% reduction in colonic PGE2. Mean colonic mucosal PGE2 concentrations were 6.55 ng/mg protein (SD, 5.78) before any supplementation and 3.59 ng/mg protein (SD, 3.29) after 12 weeks of target dosing. In secondary analyses, the decreases in PGE2 were significantly attenuated in overweight and obese participants. This occurred despite a higher target dose for the obese versus normal weight participants, as generated by the pharmacodynamic predictive model. Large decreases also were observed in 12-hydroxyicosatetraenoic acids, and PGE3 increased substantially. Future biomarker-driven dosing models for cancer prevention therefore should consider energy balance as well as overall eicosanoid homeostasis in normal tissue.

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“…5-LOX may directly control tumour cell function or indirectly affect the tumour microenvironment. Increased 5-LOX activity has been demonstrated to play a role in the early stages of colon cancer (53) and in carcinogenesis in human oral cavity tissues (54). It was also reported that 5-LOX expression may be involved in the development of BCR-ABL-induced chronic myeloid leukaemia (55).…”

Section: Loxs and Their Inhibitors In Cancer Treatmentmentioning

confidence: 97%