Oxysterol-induced Apoptosis in Human Monocytic Cell Lines

Aupeix, Karine; Weltin, D.; Mejía, José Enrique; Christ, Marielle; Marchal, Jean; Freyssinet, Jean‐Marie; Bischoff, Pierre

doi:10.1016/s0171-2985(11)80108-7

Cited by 106 publications

(75 citation statements)

References 31 publications

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“…pro-monocytic cells [11,28]. Experimental studies on vascular cells reported that equimolar amounts of 7b-OH and 7K decreased the degree of apoptosis caused by 7K alone endothelial cells and in murine J774.A1 macrophages [14,15].…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…The mode of cell death that they induce on endothelial cells [3,4], smooth muscle cells [5], and monocytic cells [6,7] present typical features of apoptosis which is a highly conserved process in various species and organs [8]. In contrast to necrosis [9], initiation of apoptosis is an active and gene-directed mode of cell death which requires de novo gene expression and new protein synthesis [10].…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis and of interleukin‐1β secretion by 7β‐hydroxycholesterol and 7‐ketocholesterol: partial inhibition by Bcl‐2 overexpression

et al. 1997

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The oxysterols, 7ß-hydroxycholesterol and 7-ketocholesterol, are involved in the cytotoxicity of oxidized LDL. To elucidate their molecular mechanisms, the human promonocytic leukemia cells U937 and U4 were used. U4 cells overexpressing Bcl-2 were obtained by transfection of U937 cells. 7ß-hydroxycholesterol and 7-ketocholesterol induced nuclear condensation and/or fragmentation, internucleosomal DNA fragmentation, and IL-lß secretion, which were partially inhibited by Bcl-2 overexpression. These findings underline that these oxysterols could constitute major risk factors in atherosclerosis by their cytotoxicity and their ability to induce IL-lß release which might favor the recruitment of immunocompetent cells in the atherosclerotic plaque.

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“…25-OHC has been used extensively as a model oxysterol compound in studies of both oxysterol toxicity and cellular cholesterol homeostasis. 25-OHC induces apoptosis in cultured monocyte-macrophages (13,24,25) and lymphoid cell lines (26,27) in the range of 1-10 M. The concentrations of oxysterols used to induce apoptosis in these in vitro studies are below the upper limit of the physiological concentration of oxysterols detected in human plasma after the ingestion of a test meal, which has been reported to be as high as 37 M (28), and are within the range of oxysterols most commonly detected in plasma of individuals with hypercholesterolemia, 10-30 M (29-31). Like Ox-LDL, oxysterols induce the release of cytochrome c from mitochondria (32,33), the hallmark of the mitochondrial apoptosis pathway.…”

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confidence: 99%

Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages

Freeman

Rusiñol

Linton

et al. 2005

Journal of Lipid Research

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Oxysterol-induced Apoptosis in Human Monocytic Cell Lines

Cited by 106 publications

References 31 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

Induction of apoptosis and of interleukin‐1β secretion by 7β‐hydroxycholesterol and 7‐ketocholesterol: partial inhibition by Bcl‐2 overexpression

Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages

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