Biological effects of oxysterols: Current status

Guardiola, Francesc; Codony, R.; Addis, P. B.; Rafecas, Magda; Boatella, Josep

doi:10.1016/0278-6915(95)00094-1

Cited by 286 publications

(190 citation statements)

References 142 publications

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“…24 Furthermore, numerous studies reported atherogenic 25,26 and cytotoxic properties [27][28][29][30] of cholesterol oxides, leading to apoptosis or necrosis in various cell types. 24,[31][32][33] They may also exert their effects by lowering cholesterol availability for cell membrane formation by inhibiting 3-hydroxy-methylglutaryl coenzyme A reductase (HMG-CoA reductase), a key enzyme in cholesterol synthesis. 34 Cholesterol oxides bind to specific membrane receptors or cytosolic binding proteins, leading to the perturbation of cholesterol synthesis.…”

Section: Introductionmentioning

confidence: 99%

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

et al. 2004

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Plant sterols are found in fruits and vegetables. Their cholesterol-lowering effect is well documented. Our study aimed at comparing antiproliferative effects of 7b-hydroxysitosterol (7b-OHsito) versus 7b-hydroxycholesterol (7b-OHchol) on the human colon cancer cell line Caco-2. When cells were exposed for 32 h to 60 lM 7b-OHsito or to 30 lM 7b-OHchol, both compounds caused 50% growth inhibition. Cells treated with 7b-OHsito showed enhanced caspase-9 and -3 activities followed by DNA fragmentation. In contrast, 7b-OHchol did not activate caspase-3 and activation of caspase-9 and DNA fragmentation were delayed. The treatment of cells with the caspase inhibitor Z-VAD.fmk retarded the 7b-OHsito-induced apoptotic process but not that triggered by 7b-OHchol. Our data suggest that the two compounds in spite of their structural similarities target different cellular pathways, which lead to cell death.

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Section: Introductionmentioning

confidence: 99%

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

et al. 2004

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“…Oxysterols are able to elicit changes in cholesterol synthesis, cell growth, and membrane composition, and can cause immunosuppression (3)(4)(5)(6)(7)(8). These activities have led to many studies of oxysterols, usually as toxins in the environment and foods (9,10), or as implicated in atherosclerosis (11)(12)(13)(14).…”

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confidence: 99%

Structure‐apoptotic potency evaluations of novel sterols using human leukemic cells

Johnson

Russell

Крылов

et al. 2000

Lipids

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Three oxidized analogs of cholesterol have been characterized for their ability to cause apoptotic cell death in CEM-C7-14 human leukemic cells. In addition to testing 15-ketocholestenol (K15), 15-ketocholestenol hydroxyethyl ether (CK15), and 7-ketocholesterol hydroxyethyl ether (CK7), an oxysterol of known apoptotic response, 25-hydroxycholesterol (25OHC), served as a standard for comparison. Growth studies based on dye exclusion by viable cells while using a sublethal concentration of oxysterols ranked their potency for cell kill as 25OHC > K15 > CK15 > CK7. Both the TUNEL assay (terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling), which quantifies the amount of DNA nicks caused by a toxic agent, and the MTT assay, which measures cell metabolism and thus reflects cell viability, substantiated the same rank order. An ELISA assay for evaluating release of DNA fragments into the cytosol after treatment gave a similar potency order. The oncogene c-myc mRNA was suppressed by all three oxysterols, with 25OHC and K15 being the most potent suppressors. Hoechst and Annexin V staining documented that these oxysterols kill cells by an apoptotic pathway as evidenced by condensation of nuclear chromatin and plasma membrane inversion, respectively. From these in vitro studies, we believe that 25OHC, K15, and possibly CK15 have the potential to be chemotherapeutic agents.Paper no. L8259 in Lipids 35, 305-315 (March 2000).Both glucocorticoids and oxysterols can cause apoptosis of certain cells. For this action, glucocorticoids require a specific cytosolic protein, the glucocorticoid receptor (GR). No oxysterol receptor has been unequivocally identified, although two cellular proteins do specifically bind oxysterols: the oxysterol binding protein (OBP) and LXR, a member of the nuclear receptor family of proteins. As yet it is not certain that either protein is required for oxysterols' apoptotic actions. In our test system, the human leukemic cell line CEM, analysis of the events following addition of either class of steroid shows similarities at several points. These include a delay of about 1 d before the activation of caspases and nucleases, which occurs around the time of overt apoptosis. During this initial phase of cell death when the steroidal effects can be reversed, both types of steroids cause profound suppression of the oncogene product, cMyc (1,2). Because of their apoptotic action, glucocorticoids are used widely as antileukemic drugs. The similarity of effects of oxysterols suggests that they also might have therapeutic usefulness, alone, or in conjunction with glucocorticoids. Oxysterols are able to elicit changes in cholesterol synthesis, cell growth, and membrane composition, and can cause immunosuppression (3-8). These activities have led to many studies of oxysterols, usually as toxins in the environment and foods (9,10), or as implicated in atherosclerosis (11-14). The relatively greater sensitivity of certain malignant, as opposed to normal, cells offers an opportunity to use...

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“…Esses relatos aparecem em várias revisões feitas (Smith, Johnson, 1989;Kumar & Signal, 1991;Bösinguer et al, 1993;Addis et al, 1996;Guardiola et al, 1996;, que demonstram que estes compostos são responsáveis por alguns dos efeitos biológicos tradicionalmente atribuídos ao colesterol.…”

Section: Efeitos Biológicos De óXidos De Colesterolunclassified

“…A oxidação da LDL estimula sua captação por receptores macrofágicos "scavenger", levando ao desenvolvimento das células espumosas, pelo acúmulo de colesterol esterificado (Oliveira, Quintão, 1992). A supressão da captação da LDL, pela inibição da expressão do gene receptor de LDL, tem sido observada em relação ao 7-Ceto, 25-OH, 5,6-epóxidos e Triol (Peng et al, 1991;Guardiola et al, 1996). Além disso, alguns OsC aumentam a transcrição do gene ABC-1 ("ATP -Binding Cassette Transporter-1") que codifica o transportador de membrana ABCA-1.…”

Section: Efeitos Biológicos De óXidos De Colesterolunclassified

Óxidos de colesterol: ocorrência em alimentos, formação e efeitos biológicos

Morales-Aizpurúa¹,

Tenuta-Filho²

2002

Rev. Bras. Cienc. Farm.

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Foram revisadas questões importantes envolvendo a ocorrência de óxidos de colesterol - INTRODUÇÃOO colesterol é um composto lipídico insaturado, instável e suscetível à oxidação, sendo o processo oxidativo influenciado por muitos outros fatores, além da participação do oxigênio. Por sua vez, muitos dos óxidos de colesterol -OsC -correspondentemente formados são substâncias de interesse químico, bioquímico, farmacológico, toxicológico, tecnológico e também clínico, pela relação com processos citotóxicos, angiotóxicos, aterogênicos, mutagênicos e carcinogênicos.Por essa razão a ocorrência de OsC verificada em alimentos é de particular importância, sendo óbvio então que a oxidação do colesterol deva ser evitada. O perfil dos óxidos formados e as quantidades correspondentes também são definidos pelas características do alimento e interações entre seus componentes e produtos de decomposição, durante o processamento e/ou armazenamento.Neste trabalho de revisão foram abordadas questões relativas à oxidação do colesterol, enfocando aspectos da ocorrência de OsC em alimentos, sua formação e efeitos biológicos. ÓXIDOS DE COLESTEROL -OsCO colesterol (5-colesten-3β-ol) apresenta uma dupla ligação entre os carbonos 5 e 6 do anel B, que o torna susceptível à oxidação. Os OsC são similares ao colesterol. Apresentam em comum a estrutura básica do núcleo ciclopentano-per-hidro-fenantreno, formado por quatro anéis condensados de hidrocarboneto (A-D), com caráter apolar e insolúvel em água, e uma cadeia lateral ramificada de hidrocarboneto unida ao carbono 17 do núcleo esteróide, também apolar e insolúvel em água. Há um grupo hidroxila no C-3, do anel A, em configuração beta, de caráter polar, que confere alguma afinidade com o meio aquoso e capacidade de esterificação com ácidos graxos, convertendo-se, neste caso, em totalmente insolú-

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Biological effects of oxysterols: Current status

Cited by 286 publications

References 142 publications

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

Structure‐apoptotic potency evaluations of novel sterols using human leukemic cells

Óxidos de colesterol: ocorrência em alimentos, formação e efeitos biológicos

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