Oxidized Derivatives of Dihydrobrassicasterol: Cytotoxic and Apoptotic Potential in U937 and HepG2 Cells

Kenny, Olivia; O’Callaghan, Yvonne C.; O’Connell, Niamh M; McCarthy, Florence O.; Maguire, Anita R.; O’Brien, Nora M.

doi:10.1021/jf204737e

Cited by 19 publications

(10 citation statements)

References 40 publications

(128 reference statements)

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“…Similar results were obtained in Caco-2 cells treated with 30 mM 7b-OH that inhibited cell growth by 50% at 32 h incubation and induced apoptosis, but in this case caspase-3 activity remained within control range during the whole observation time (72 h) [25]. In another study 30 mM of individual oxysterol components in the diet has shown that all a-epox, b-epox, 7K, and 7b-OH significantly reduced U937 viability and increased caspase activities and DNA fragmentation [26]. Very high concentrations of 7K (up to 120 mM) altered mitochondrial permeability and the relative distribution of total RNA in G1 and G2 phases of the cell cycle in 6 days plated CaCo-2 cells [27].…”

Section: Discussionmentioning

confidence: 91%

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: 91%

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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“…Previous studies have demonstrated that POPs are associated with apoptosis [ 10 ], atherosclerosis, cytotoxicity, and inflammation [ 11 ]. Recent studies have found that the triol derivatives are the most cytotoxic, while 7β-hydroxy and 7-keto derivatives are effective in inducing apoptosis in U937 cells [ 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Thermal-Oxidation Stability of Soybean Germ Phytosterols in Different Lipid Matrixes

Chen

Tang

et al. 2020

Molecules

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The stability of soybean germ phytosterols (SGPs) in different lipid matrixes, including soybean germ oil, olive oil, and lard, was studied at 120, 150, and 180 °C. Results on the loss rate demonstrated that SGPs were most stable in olive oil, followed by soybean germ oil, and lard in a decreasing order. It is most likely that unsaturated fatty acids could oxidize first, compete with consumption of oxygen, and then spare phytosterols from oxidation. The oxidation products of SGPS in non-oil and oil systems were also quantified. The results demonstrated that at relatively lower temperatures (120 and 150 °C), SGPs’ oxidation products were produced the most in the non-oil system, followed by lard, soybean germ oil, and olive oil. This was consistent with the loss rate pattern of SGPs. At a relatively higher temperature of 180 °C, the formation of SGPs’ oxidation products in soybean germ oil was quantitatively the same as that in lard, implying that the temperature became a dominative factor rather than the content of unsaturated fatty acids of lipid matrixes in the oxidation of SGPs.

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“…Even though POPs have been associated with atherosclerosis diseases and cytotoxic effects, this has only been found at concentrations [5, 6]. Due to the ability of phytosterol compounds to reduce plasma serum cholesterol levels in humans, their addition to foods has increased significantly over the past decade [7]. However, there is some concern as these compounds showed cytotoxic activity towards normal cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of Sterols Isolated fromMyrtillocactus geometrizanson Growth Inhibition of Colon and Breast Cancer Cells

Bolaños-Carrillo

Ventura-Gallegos

Saldivar-Jiménez

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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Objective. To explore the effect of peniocerol and macdougallin on HCT-15 and MCF-7 cells proliferation, cell cycle, apoptosis, and PARP cleavage. Methods. HCT-15 and MCF-7 cells were treated with various concentrations of peniocerol and macdougallin (10–80 μM) during 24 or 48 h. Crystal Violet Assay was used to evaluate the inhibition effect. Cell cycle regulation was examined by a propidium iodide method. Cell apoptosis was detected through both Annexin–V FLUOS/PI double-labeled cytometry assays and Western blot was applied to assess PARP cleavage. Results. Peniocerol and macdougallin induced growth inhibition and apoptosis in vitro in a time- and dose-dependent manner. Moreover, peniocerol and macdougallin induced arrest of cell cycle-dependent manner and increased the proportion of cells in G0/G1 phase. PARP cleavage in HCT-15 and MCF-7 cells was induced by treatment with peniocerol and macdougallin after 36 hours. Conclusions. Our results showed that the mechanism of cytotoxicity displayed by peniocerol and macdougallin is related to cell cycle arrest and apoptosis in both cell lines. This is a significant observation because it helps to understand the way some oxysterols isolated from Myrtillocactus geometrizans develop their biological activities against cancer cells.

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Oxidized Derivatives of Dihydrobrassicasterol: Cytotoxic and Apoptotic Potential in U937 and HepG2 Cells

Cited by 19 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

Thermal-Oxidation Stability of Soybean Germ Phytosterols in Different Lipid Matrixes

Effect of Sterols Isolated fromMyrtillocactus geometrizanson Growth Inhibition of Colon and Breast Cancer Cells

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