Pro-oxidant and proapoptotic effects of cholesterol oxidation products on human colonic epithelial cells: A potential mechanism of inflammatory bowel disease progression

Biasi, Fiorella; Mascia, Cinzia; Astegiano, Marco; Chiarpotto, Elena; Nano, M; Vizio, Barbara; Leonarduzzi, Gabriella; Poli, Giuseppe

doi:10.1016/j.freeradbiomed.2009.09.020

Cited by 73 publications

(90 citation statements)

References 40 publications

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“…These findings are in agreement with our previous results showing no necrogenic action, and a moderate induction of apoptosis by 30 mM concentration of the same oxysterol mixture, in undifferentiated CaCo-2 cancer cells, compared to differentiated enterocyte-like CaCo-2 cells, which were more sensitive to the sterol challenge [9]. MTT assay showed a decrease on cell viability and proliferation following incubation with increasing concentrations of oxysterol mixture (60 mM/90 mM) (Table 1).…”

Section: Discussionsupporting

confidence: 93%

“…We determined the necrogenic effect in colon cancer CaCo-2 cells of a representative dietary mixture of oxysterols, which has very recently been shown to potentially interfere with the homeostasis of the intestinal epithelium [9,10]. The oxysterol mixture was used in concentrations corresponding to low (30 mM), moderate (60 mM) and high (90 mM) daily dietary intake.…”

Section: Discussionmentioning

confidence: 99%

“…The membrane fraction was suspended in cold lysis buffer [10 mM TriseHCl pH 7.4, 1 mM EDTA, Triton X-100 0.5% (v/v)] for 20 min. Immunoprecipitation and immunoblotting were performed as described by Biasi et al [9]. Proteins were evaluated with the Bio-Rad protein assay dye reagent, following the Bradford method [20].…”

Section: Evaluation Of Activated Nadph Oxidase Complex By Immunoblottingmentioning

confidence: 99%

“…In previous work, we found that challenging CaCo-2 cells with a representative mixture of the oxysterols most commonly found in cholesterol-rich foodstuffs may contribute to oxidative unbalance by inducing the generation of reactive oxygen species (ROS) through upregulation of the colonic NADPH-oxidase isoform NOX1 [9,10]. Interestingly, oxysterols exert their biological action in ways that differ depending on the degree of cell differentiation (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, oxysterols exert their biological action in ways that differ depending on the degree of cell differentiation (i.e. normal enterocytelike CaCo-2 cells, or the undifferentiated CaCo-2 cell line) [9].…”

Section: Introductionmentioning

confidence: 99%

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Evidence of cell damage induced by major components of a diet-compatible mixture of oxysterols in human colon cancer CaCo-2 cell line

et al. 2013

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a b s t r a c tCholesterol oxidation products, termed oxysterols, have been shown to be more reactive than unoxidized cholesterol, possessing marked pro-inflammatory and cytotoxic effects in a number of cells and tissues. Oxysterols, absorbed with the diet as products of cholesterol auto-oxidation, have recently been suggested to potentially interfere with homeostasis of the mucosal intestinal epithelium, by promoting and sustaining irreversible damage.However, the treatment of colon cancer cells with a diet-compatible mixture of oxysterols does not elicit the same responses than individual components added to the cells at the same concentrations at which they are present in the mixture. Sixty mM oxysterol mixture showed a slight pro-apoptotic effect on human colon cancer CaCo-2 cell line, evaluated in terms of caspase-3 and caspase-7 activation; conversely, 7a-hydroxycholesterol, 7b-hydroxycholesterol and 5a,6a-epoxycholesterol were identified to be able to induce a significant pro-apoptotic effect if added to cell culture singly; 7b-hydroxycholesterol had stronger action than other compounds. The enhanced production of reactive oxygen species through up-regulation of the colonic NADPH-oxidase isoform NOX1 appeared to be the key event in oxysterolinduced apoptosis in these colon cancer cells. As regards pro-inflammatory effects of oxysterols, IL-8 and MCP-1 were evaluated for their chemotactic activity. Only MCP-1 production was significantly induced by 7b-hydroxycholesterol, as well as by cholesterol and oxysterol mixture. However, oxysterolinduced inflammation appeared to be NOX1-independent, suggesting a secondary role of this enzyme in inducing inflammation in colon cancer cells.A selective cell death induced by specific oxysterols against colon cancer cells, mainly exploiting their ability to activate NOX1 in generating oxidative reactions, might represent a promising field of investigation in colorectal cancer, and might bring new insights on strategies in anticancer therapy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of Activated Nadph Oxidase Complex By Immunoblottingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evidence of cell damage induced by major components of a diet-compatible mixture of oxysterols in human colon cancer CaCo-2 cell line

et al. 2013

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Lipid Oxidation Derived Aldehydes and Oxysterols Between Health and Disease

Sottero

Leonarduzzi

Testa

et al. 2018

Euro J Lipid Sci & Tech

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102

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Non‐enzymatic and enzymatic oxidation of lipids has long been a primary issue in human pathophysiology, with special emphasis on diet‐ and nutrition‐related aspects. While there is no doubt that the n‐3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid, and docosahexaenoic acid, exert anti‐inflammatory, inflammation resolving, and immunomodulatory effects in different model systems, their non‐enzymatic oxidation during food storage and cooking, as well as during gastrointestinal digestion, can give rise to excessive amounts of quite reactive aldehydic end‐products, in particular 4‐hydroxyhexenal. However, the non‐enzymatic oxidation of n‐6 PUFAs is, in principle, far more harmful, not least because one of its main end‐products, 4‐hydroxynonenal, has been shown to be associated with the progression of a number of human diseases. Several cholesterol oxidation products, known as oxysterols, are also of primary nutritional importance; these can be generated in the human body through both enzymatic and non‐enzymatic reactions, but may also be present in the diet in excessive amounts due to the autoxidation of cholesterol‐containing foods. Their potential contribution to the pathogenesis and progression of human diseases in which hypercholesterolemia is a primary risk factor, such as atheroclerosis, Alzheimer's disease, and some forms of cancers, has been unanimously recognized. Practical Applications: This review highlights the importance of certain lipid oxidation products, namely 4‐hydroxyalkenals and oxysterols, in the modulation of processes fundamental to human health and disease. The observations and facts reviewed here underline the need to carefully consider the pros and cons of the dietary intake and metabolic fate of n‐3 PUFA, n‐6 PUFA, and cholesterol, when producing, storing, and processing lipid‐containing food. Lipid oxidation is a common process that occurs through both enzymatic and non‐enzymatic reactions. It is responsible for the formation of several compounds, including polyunsaturated fatty acid (PUFA)‐derived 4‐hydroxyalkenals and cholesterol oxidation products, namely oxysterols. Depending on their concentrations, these molecules possess physiopathological properties involved in cell viability and function. At high concentrations, such as those resulting from intense oxidative stress or excessive fatty food intake, they are associated to the onset of many diseases. A correct diet regimen, improved food processing and storage, and suitable antioxidant supplementation, should be implemented to counteract promotion of disease development by excess oxidized lipids. (HHE, 4‐hydroxyhexenal; HNE, 4‐hydroxynonenal; ROS, reactive oxygen species).

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NADPH Oxidase System Mediates Cholesterol Secoaldehyde-Induced Oxidative Stress and Cytotoxicity in H9c2 Cardiomyocytes

Laynes

Raghavamenon

Atkins-Ball

et al. 2022

Cardiovascular Signaling in Health and Disease

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Pro-oxidant and proapoptotic effects of cholesterol oxidation products on human colonic epithelial cells: A potential mechanism of inflammatory bowel disease progression

Cited by 73 publications

References 40 publications

Evidence of cell damage induced by major components of a diet-compatible mixture of oxysterols in human colon cancer CaCo-2 cell line

Evidence of cell damage induced by major components of a diet-compatible mixture of oxysterols in human colon cancer CaCo-2 cell line

Lipid Oxidation Derived Aldehydes and Oxysterols Between Health and Disease

NADPH Oxidase System Mediates Cholesterol Secoaldehyde-Induced Oxidative Stress and Cytotoxicity in H9c2 Cardiomyocytes

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