Ethylcoprostanol modulates colorectal cancer cell proliferation and mitigates cytotoxicity of cholesterol metabolites in non-tumor colon cells

文献信息

发布日期 2023-11-15
DOI 10.1039/D3FO01868G
影响因子 5.396
作者

Mussa Makran, Guadalupe Garcia-Llatas, Amparo Alegría, Antonio Cilla


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摘要

Sterols can be metabolized by gut microbiota. The cholesterol metabolites have been proposed as promoters of colorectal cancer (CRC), while the effect of plant sterol metabolites is unknown. This study aimed to evaluate the cytotoxicity of metabolites from cholesterol (coprostanol, cholestanol, coprostanone and cholestenone) and β-sitosterol (ethylcoprostanol) on human colon tumor (Caco-2) and non-tumor (CCD-18Co) cells at physiological concentrations (9–300 μM) and exposure time (24 h). Ethylcoprostanol reduced the tumor cell proliferation (MTT), showing in flow cytometry assays induction of apoptosis via production of reactive oxygen species (ROS) and ceramide. Transcriptomic analysis (qPCR) showed activation of the intrinsic apoptosis pathway (BAX/BCL2 ratio and CASP9 increased), accompanied by downregulation of the p21 gene. Cholesterol metabolites, mainly the most hydrophobic, induced apoptosis and G0/G1 phase arrest in non-tumor cells through overproduction of ROS. Both the intrinsic and extrinsic (CASP8 increased) apoptosis pathways occurred. In turn, a reduction in the expression of the cyclin E1 gene confirmed the cell cycle arrest. In addition, ethylcoprostanol protected non-tumor cells from the most cytotoxic cholesterol metabolite (cholestenone). In conclusion, ethylcoprostanol is a promising candidate as a therapeutic adjuvant in CRC, while cholesterol metabolites could act as CRC promoters through their cytotoxicity.

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Food & Function

Food & Function
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Food & Function provides a unique venue for physicists, chemists, biochemists, nutritionists and other food scientists to publish novel, cutting-edge, original research focussing on food, its nutrients and their relation to human health and nutrition. We welcome research describing the: Physical properties and structure of food and how this relates to sensory perception and human health Biochemical and physiological actions of food components Interactions between foods, gut microbiota and human physiology Nutritional and biological evaluation of food Clinical and population studies using food or food components Development of biomarkers of food intake and effects on human health We also welcome systematic reviews and meta-analyses of existing studies in the literature, provided these are objective and scientifically valid Food in this context is defined as materials of plant, animal or mineral origin, which are consumed orally (by humans) for pleasure and to sustain growth and vital processes. Examples of research topics that are of interest to be published in Food & Function are: Chemistry and physics of food components and digestion processes Relationship between the physical properties/structure of food and nutrition and human health - for example, impact of food matrix or processing on nutrient release and uptake Molecular properties and physiological effects of food components (nutrients, fibres, essential micronutrients, phytochemicals, bioactives, food substitutes, novel ingredients, allergens, flavours and fragrances) Nutritional and health effects of food including bioavailability and metabolism assessment of food components (nutrients, micronutrients and other microconstituents) Efficacy and mechanisms of food constituents in the body - including biomarkers of intakes, exposure and effects Impacts of foods/food components on gut microorganisms and human physiology - For example impact of fermented foods Role of nutrition and diet in human disease prevention and development Cellular and molecular effects/mechanisms of food/food components image block The following types of research are not within the scope of Food & Function: Research relating to traditional herbal medicines, medicinal plants or active compounds extracted from such plants (materials that are primarily consumed as medicine, i.e. the intended purpose is primarily to treat, cure or prevent a non-deficiency disease) or relating to foods not recognised as human diet contributors Animal nutrition research that is not primarily designed as a model to benefit human nutrition (for example, studies of growth/accretion, heat stress, weaning, ruminant digestion, meat quality, etc.) Treatments administered by non-oral routes such as injection (subcutaneous, intramuscular, intraperitoneal, etc.), dermal/transdermal, rectal, inhalation, nasal, etc. Exceptions are when such routes of administration are used for mechanistic/control purposes in the experimental design Pharmacological/pharmaceutical approaches: Encapsulation, emulsification and/or pure controlled release of compounds or bioactives that do not come directly from edible foods, such as dietary supplements - these are better suited to a pharmaceutical journal In vitro or in vivo studies with poorly defined (insufficiently characterised) extracts and studies without appropriate controls will not be considered Cells studies not considering the metabolism of food components ingested – for example, irrelevant exposure of cells to compounds not present in the body after absorption Manuscripts with only a fully theoretical/bioinformatic approach and without appropriate support from analytical evidence will not be considered for publication Studies focussing solely on food engineering, preservation and sustainable technologies – these can be published in our companion journal Sustainable Food Technology Pure food analysis - these can be published in Analytical Methods

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