ω‐6 Polyunsaturated fatty acid γ‐linolenic acid (18:3n‐6) is a selective estrogen‐response modulator in human breast cancer cells: γ‐Linolenic acid antagonizes estrogen receptor‐dependent transcriptional activity, transcriptionally represses estrogen receptor expression and synergistically enhances tamoxifen and ICI 182,780 (Faslodex) efficacy in human breast cancer cells

Menendez, Javier A.; Colomer, Ramón; Lupu, Ruth

doi:10.1002/ijc.20096

Cited by 26 publications

(11 citation statements)

References 15 publications

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“…GLA has been shown to exert tumoricidal activity against a variety of cancers including cancers of breast, pancreas, colon, brain, etc. [17,21,22,37,38]. GLA also inhibits metastasis of cancer cells [22,[39][40][41].…”

Section: Gla and Cancermentioning

confidence: 99%

Gamma Linolenic Acid: An Antiinflammatory Omega-6 Fatty Acid

Kapoor¹,

Huang²

2006

CPB

293

160

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Inflammation plays an important role in health and disease. Most of the chronic diseases of modern society, including cancer, diabetes, heart disease, arthritis, Alzheimer's disease, etc. have inflammatory component. At the same time, the link between diet and disease is also being recognized. Amongst dietary constituents, fat has gained most recognition in affecting health. Saturated and trans fatty acids have been implicated in obesity, heart disease, diabetes and cancer while polyunsaturated fatty acids (PUFAs) generally have a positive effect on health. The PUFAs of omega-3 and omega-6 series play a significant role in health and disease by generating potent modulatory molecules for inflammatory responses, including eicosanoids (prostaglandins, and leukotrienes), and cytokines (interleukins) and affecting the gene expression of various bioactive molecules. Gamma linolenic acid (GLA, all cis 6, 9, 12-Octadecatrienoic acid, C18:3, n-6), is produced in the body from linoleic acid (all cis 6,9-octadecadienoic acid), an essential fatty acid of omega-6 series by the enzyme delta-6-desaturase. Preformed GLA is present in trace amounts in green leafy vegetables and in nuts. The most significant source of GLA for infants is breast milk. GLA is further metabolized to dihomogamma linlenic acid (DGLA) which undergoes oxidative metabolism by cyclooxygenases and lipoxygenases to produce anti-inflammatory eicosanoids (prostaglandins of series 1 and leukotrienes of series 3). GLA and its metabolites also affect expression of various genes where by regulating the levels of gene products including matrix proteins. These gene products play a significant role in immune functions and also in cell death (apoptosis). The present review will emphasize the role of GLA in modulating inflammatory response, and hence its potential applications as an anti-inflammatory nutrient or adjuvant.

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Section: Gla and Cancermentioning

confidence: 99%

Gamma Linolenic Acid: An Antiinflammatory Omega-6 Fatty Acid

Kapoor¹,

Huang²

2006

CPB

293

160

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“…Some lignans and essential fatty acids have ERα agonist potencies similar to the lower-potency soy isoflavones based on binding affinities and cellular responses (Jin et al 2013 ; Liu et al 2004 ; Pianjing et al 2011 ; Rose and Connolly 1989 ; Menendez et al 2004 ). Although their agonistic interactions with ERα are detectable in the highly sensitive ERαTA (Table 1 : enterolactone, enterodiol, sesamin, sesamol, sesamolin) and the in vivo uterotrophic assay (Penttinen-Damdimopoulou et al 2009 ), their mechanistic potencies appear to be too low to produce overt physiological effects in either rodents or humans (Table 3 ).…”

Section: Comparison Of Mechanistic Potencies To Clinical Endpointsmentioning

confidence: 99%

Human-relevant potency threshold (HRPT) for ERα agonism

Borgert¹,

Matthews

Baker

2018

Arch Toxicol

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The European Commission has recently proposed draft criteria for the identification of endocrine disrupting chemicals (EDCs) that pose a significant hazard to humans or the environment. Identifying and characterizing toxic hazards based on the manner by which adverse effects are produced rather than on the nature of those adverse effects departs from traditional practice and requires a proper interpretation of the evidence regarding the chemical’s ability to produce physiological effect(s) via a specific mode of action (MoA). The ability of any chemical to produce a physiological effect depends on its pharmacokinetics and the potency by which it acts via the various MoAs that can lead to the particular effect. A chemical’s potency for a specific MoA—its mechanistic potency—is determined by two properties: (1) its affinity for the functional components that comprise the MoA, i.e., its specific receptors, enzymes, transporters, transcriptional elements, etc., and (2) its ability to alter the functional state of those components (activity). Using the agonist MoA via estrogen receptor alpha, we illustrate an empirical method for determining a human-relevant potency threshold (HRPT), defined as the minimum level of mechanistic potency necessary for a chemical to be able to act via a particular MoA in humans. One important use for an HRPT is to distinguish between chemicals that may be capable of, versus those likely to be incapable of, producing adverse effects in humans via the specified MoA. The method involves comparing chemicals that have different ERα agonist potencies with the ability of those chemicals to produce ERα-mediated agonist responses in human clinical trials. Based on this approach, we propose an HRPT for ERα agonism of 1E-04 relative to the potency of the endogenous estrogenic hormone 17β-estradiol or the pharmaceutical estrogen, 17α-ethinylestradiol. This approach provides a practical way to address Hazard Identification according to the draft criteria for identification of EDCs recently proposed by the European Commission.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2186-z) contains supplementary material, which is available to authorized users.

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“…These authors further reported that female mice fed diets enriched with u-6 polyunsaturated fatty acid produced a highly significant excess of female offspring . It is established that u-6 polyunsaturated fatty acid has anti-oestrogenic properties (Menendez et al 2004).…”

Section: Age Of Maturation In Gerbilsmentioning

confidence: 99%