The estrogenic effect of trigonelline and 3,3-diindolymethane on cell growth in non-malignant colonocytes

Yoo, Gyhye; Allred, Clinton D.

doi:10.1016/j.fct.2015.11.015

Cited by 16 publications

(7 citation statements)

References 43 publications

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“…[ 26,41 ] The biological effects associated with trigonelline or N ‐methylpyridinium have been generally obtained by exposing cell lines to concentrations not in line with the physiological concentrations reachable in normal coffee consumption settings. Some positive results on antioxidant activity, on functional neurite outgrowth or on dopamine release have been obtained using trigonelline concentrations comparable to those recorded for the 3C group, [ 42 ] whereas chemopreventive properties [ 43 ] and estrogenic activity [ 44,45 ] were observed for trigonelline using nano‐ to picomolar concentrations. Generally, concentrations higher than 10 µmol L −1 for trigonelline and 1 µmol L −1 or N ‐methylpyridinium [ 8,43,46–49 ] should be considered too high in common daily coffee intake scenarios.…”

Section: Discussionmentioning

confidence: 93%

Absorption, Pharmacokinetics, and Urinary Excretion of Pyridines After Consumption of Coffee and Cocoa‐Based Products Containing Coffee in a Repeated Dose, Crossover Human Intervention Study

Bresciani

Tassotti

Rosi

et al. 2020

Molecular Nutrition Food Res

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Scope The present study assesses the absorption, pharmacokinetics, and urinary excretion of coffee pyridines and their metabolites after daily regular exposure to specific dosages of coffee or cocoa‐based products containing coffee (CBPCC), considering different patterns of consumption. Methods and results In a three‐arm, crossover, randomized trial, 21 volunteers are requested to randomly consume for 1 month: one cup of espresso coffee per day, three cups of espresso coffee per day, or one cup of espresso coffee plus two CBPCC twice per day. The last day of the one‐month treatment, blood and urine samples are collected for 24 h. Trigonelline, N‐methylpyridinium, N‐methylnicotinamide, and N‐methyl‐4‐pyridone‐5‐carboxamide are quantified. Trigonelline and N‐methylpyridinium absorption curves and 24‐h urinary excretion reflect the daily consumption of different servings of coffee or CBPCC, showing also significant differences in main pharmacokinetic parameters. Moreover, inter‐subject variability due to sex and smoking is assessed, showing sex‐related differences in the metabolism of trigonelline and smoking‐related ones for N‐methylpyridinium. Conclusion The daily exposure to coffee pyridines after consumption of different coffee dosages in a real‐life setting is established. This data will be useful for future studies aiming at evaluating the bioactivity of coffee‐derived circulating metabolites in cell experiments, mimicking more realistic experimental conditions.

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Section: Discussionmentioning

confidence: 93%

Absorption, Pharmacokinetics, and Urinary Excretion of Pyridines After Consumption of Coffee and Cocoa‐Based Products Containing Coffee in a Repeated Dose, Crossover Human Intervention Study

Bresciani

Tassotti

Rosi

et al. 2020

Molecular Nutrition Food Res

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“…DIM has been reported to have anticancer effects in colon cancer cells by enhancing the ER-mediated transcriptional activity and the upregulation of apoptosisrelated genes. 28 The diphenyl derivative of DIM induced apoptosis in breast cancer cells by blocking EGFR pathway downstream molecules such as STAT3, Akt, and ERK1/2. 29 A dibromo derivative of DIM induced caspasemediated apoptosis in squamous carcinoma cells by mediating the p38 MAPK pathway.…”

Section: Discussionmentioning

confidence: 99%

Studies on the mode of action of synthetic diindolylmethane derivatives against triple negative breast cancer cells

Shilpa

Lakshmi

Jamsheena

et al. 2022

Basic Clin Pharma Tox

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Diindolylmethane (DIM) is a metabolic product of indole‐3‐carbinol (I3C), the major phytochemicals present in cruciferous vegetables, which can modulate multiple signalling pathways in cancer. The present study deals with the mechanism of action of two synthetic biaryl conjugates of DIM in triple negative breast cancer cells. Out of 12 DIM derivatives tested, two compounds, DIM‐1 and DIM‐4, exhibit cytotoxicity with GI50 values of 9.83 ± 0.2195 μM and 8.726 ± 0.5234 μM, respectively, in 2D culture. In 3D culture, DIM‐1 and DIM‐4 show GI50 values of 24.000 ± 0.7240 μM and 19.230 ± 0.3754 μM, respectively. The non‐toxic nature of the compounds was also established by the toxicity studies using the zebrafish model system. The two compounds induced apoptosis and anoikis in the cancer cells, which was confirmed by morphological analysis, nuclear fragmentation, membrane integrity assay, caspase activity measurements and modulation of pro/anti‐apoptotic proteins. The compounds inhibited cell migration and MMP‐2 and MMP‐9 activities indicating their anti‐metastatic property. They also reduced the expression of active Ras, phosphorylated forms of PI3K, Akt and mTOR. Immunofluorescence studies revealed the reduced expression of EGFR and pEGFR in treated cells. To conclude, DIM‐1 and DIM‐4 induced anti‐breast cancer effects by blocking EGF receptor and subsequently inhibiting Ras‐mediated PI3K‐Akt–mTOR signalling pathway.

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“…Caffeine is a well-known constituent in coffee and is known for its health benefits due to its estrogenic effects; neuroprotective effects by estrogenic activity [69] and cancer chemopreventive effects by anti-estrogenic activity [70], for example. Other nitrogenous compounds, including their derivatives, such as nicotinic acid (niacin), serotonin amides, theophylline, and trigonelline, are also estrogenic/anti-estrogenic and may function in cardioprotection, neuroprotection, cancer chemoprevention, and bone protection [71,72,73,74,76,77]. Note that the effects vary depending on differences in signaling pathways and experimental conditions, and therefore result in estrogenic or anti-estrogenic effects (see Section 2.2).…”

Section: Estrogenic Activity Of Coffee Constituentsmentioning

confidence: 99%

“…Trigonelline activated ER and stimulated the growth of estrogen-dependent breast cancer cells in vitro. However, there was no clear estrogenic activity in vivo or trigonelline did not compete against E 2 in vitro, suggesting the activation to be mediated by a separate mechanism involving new signal mediators [62,77].…”

Section: Prospective Of Estrogenic Coffee Constituentsmentioning

confidence: 99%

Estrogenic Activity of Coffee Constituents

Kiyama

2019

Nutrients

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Here, the constituents of coffee with estrogenic activity are summarized by a comprehensive literature search, and their mechanisms of action for their physiological effects are discussed at the molecular and cellular levels. The estrogenic activity of coffee constituents, such as acids, caramelized products, carbohydrates, lignin, minerals, nitrogenous compounds, oil (lipids), and others, such as volatile compounds, was first evaluated by activity assays, such as animal tests, cell assay, ligand-binding assay, protein assay, reporter-gene assay, transcription assay, and yeast two-hybrid assay. Second, the health benefits associated with the estrogenic coffee constituents, such as bone protection, cancer treatment/prevention, cardioprotection, neuroprotection, and the improvement of menopausal syndromes, were summarized, including their potential therapeutic/clinical applications. Inconsistent results regarding mixed estrogenic/anti-estrogenic/non-estrogenic or biphasic activity, and unbeneficial effects associated with the constituents, such as endocrine disruption, increase the complexity of the effects of estrogenic coffee constituents. However, as the increase of the knowledge about estrogenic cell signaling, such as the types of specific signaling pathways, selective modulations of cell signaling, signal crosstalk, and intercellular/intracellular networks, pathway-based assessment will become a more realistic means in the future to more reliably evaluate the beneficial applications of estrogenic coffee constituents.

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The estrogenic effect of trigonelline and 3,3-diindolymethane on cell growth in non-malignant colonocytes

Cited by 16 publications

References 43 publications

Absorption, Pharmacokinetics, and Urinary Excretion of Pyridines After Consumption of Coffee and Cocoa‐Based Products Containing Coffee in a Repeated Dose, Crossover Human Intervention Study

Absorption, Pharmacokinetics, and Urinary Excretion of Pyridines After Consumption of Coffee and Cocoa‐Based Products Containing Coffee in a Repeated Dose, Crossover Human Intervention Study

Studies on the mode of action of synthetic diindolylmethane derivatives against triple negative breast cancer cells

Estrogenic Activity of Coffee Constituents

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