Anti‐Androgenic Activity of Fatty Acids

Liu, Jie; Shimizu, Kuniyoshi; Kondo, Ryuichiro

doi:10.1002/cbdv.200800125

Cited by 45 publications

(39 citation statements)

References 26 publications

(34 reference statements)

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“…Furthermore, the OR51E1 agonist NA possesses the ability to reduce 5α-reductase activity and thus has anti-androgenic potential [85]. This potential might further enhance the NA-mediated effects observed in our study.…”

Section: Discussionmentioning

confidence: 57%

The activation of OR51E1 causes growth suppression of human prostate cancer cells

et al. 2016

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The development of prostate cancer (PCa) is regulated by the androgen-dependent activity of the androgen receptor (AR). Androgen-deprivation therapy (ADT) is therefore the gold standard treatment to suppress malignant progression of PCa. Nevertheless, due to the development of castration resistance, recurrence of disease after initial response to ADT is a major obstacle to successful treatment. As G-protein coupled receptors play a fundamental role in PCa physiology, they might represent promising alternative or combinatorial targets for advanced diseases. Here, we verified gene expression of the olfactory receptors (ORs) OR51E1 [prostate-specific G-protein coupled receptor 2 (PSGR2)] and OR51E2 (PSGR) in human PCa tissue by RNA-Seq analysis and RT-PCR and elucidated the subcellular localization of both receptor proteins in human prostate tissue. The OR51E1 agonist nonanoic acid (NA) leads to the phosphorylation of various protein kinases and growth suppression of the PCa cell line LNCaP. Furthermore, treatment with NA causes reduction of androgen-mediated AR target gene expression. Interestingly, NA induces cellular senescence, which coincides with reduced E2F1 mRNA levels. In contrast, treatment with the structurally related compound 1-nonanol or the OR2AG1 agonist amyl butyrate, neither of which activates OR51E1, did not lead to reduced cell growth or an induction of cellular senescence. However, decanoic acid, another OR51E1 agonist, also induces cellular senescence. Thus, our results suggest the involvement of OR51E1 in growth processes of PCa cells and its impact on AR-mediated signaling. These findings provide novel evidences to support the functional importance of ORs in PCa pathogenesis.

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Section: Discussionmentioning

confidence: 57%

The activation of OR51E1 causes growth suppression of human prostate cancer cells

et al. 2016

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“…At higher concentrations (400 μM) OA diminished cell proliferation soon after treatment as recorded by using the real-time cellular analysis (Figure 5). A similar concentration of OA (500 μM) influenced cell proliferation in a different manner depending on cell type: it inhibited cell growth on LNCaP prostate cells, it enhanced cell proliferation in case of breast cancer cell lines (MCF-7 and MDA-MB-231) and it had no effect on a non-tumorogenic epithelial cell line (MCF10A) [34, 35]. Our results showed no benefit using OA along with irradiation.…”

Section: Discussionmentioning

confidence: 68%

Combination of unsaturated fatty acids and ionizing radiation on human glioma cells: cellular, biochemical and gene expression analysis

Antal

Hackler²,

Shen

et al. 2014

Lipids Health Dis

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BackgroundBased on previous observations a potential resort in the therapy of the particularly radioresistant glioma would be its treatment with unsaturated fatty acids (UFAs) combined with irradiation.MethodsWe evaluated the effect of different UFAs (arachidonic acid (AA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and oleic acid (OA)) on human U87 MG glioma cell line by classical biochemical end-point assays, impedance-based, real-time cellular and holographic microscopic analysis. We further analyzed AA, DHA, and GLA at morphological, gene and miRNA expression level.ResultsCorresponding to LDH-, MTS assays and real-time cytoxicity profiles AA, DHA, and GLA enhanced the radio sensitivity of glioma cells. The collective application of polyunsaturated fatty acids (PUFAs) and irradiation significantly changed the expression of EGR1, TNF-α, NOTCH1, c-MYC, TP53, HMOX1, AKR1C1, NQO1, while up-regulation of GADD45A, EGR1, GRP78, DDIT3, c-MYC, FOSL1 were recorded both in response to PUFA treatment or irradiation alone. Among the analyzed miRNAs miR-146 and miR-181a were induced by DHA treatment. Overexpression of miR-146 was also detected by combined treatment of GLA and irradiation.ConclusionsBecause PUFAs increased the radio responsiveness of glioma cells as assessed by biochemical and cellular assays, they might increase the therapeutic efficacy of radiation in treatment of gliomas. We demonstrated that treatment with DHA, AA and GLA as adjunct to irradiation up-regulated the expression of oxidative-stress and endoplasmic reticulum stress related genes, and affected NOTCH1 expression, which could explain their additive effects.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-511X-13-142) contains supplementary material, which is available to authorized users.

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“…These anti-androgenic effects have been attributed to several compounds, including the phytosterol β-sitosterol (Schleich et al 2006), fatty acids (Liu et al 2009) and phenolic acids (Sanderson et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Assessment of hormone-like activities inGinkgo biloba,Elettaria cardamomumandPlantago ovataextracts usingin vitroreceptor-specific bioassays

Real

Molina-Molina

Jimenez³

et al. 2015

Food Additives & Contaminants: Part A

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Medicinal plants are widely used for the treatment of diseases and for the development of new drugs. This study was designed to determine the presence of hormone-like activities dependent on the activation of human estrogen receptor alpha (hERa) and/or androgen receptor (hAR) in methanol extracts prepared from three medicinal plants historically and currently used for therapeutic purposes: Ginkgo biloba leaves (GBL), Elettaria cardamomum seeds (ECS) and Plantago ovata seeds (POS). After a solid-liquid extraction (SLE) step, their effects on hERa function were assessed in MCF-7 breast cancer cells using the E-Screen bioassay, and their ability to induce hAR-mediated reporter gene expression was evaluated using the androgen-sensitive stable prostatic PALM cell line. Unlike POS extracts, GBL and ECS extracts showed estrogenic (0.07 and 0.20 nM E2Eq mg(-1), respectively) and anti-estrogenic (0.01 and 0.02 μM ICI182780Eq mg(-1), respectively) activities. ECS extracts evidenced androgenic activity (0.30 nM R1881Eq mg(-1)) and POS extracts anti-androgenic activity (22.30 μM ProcEq mg(-1)). According to these findings, these plant extracts may interfere with the endocrine system via one or more hormonal receptors, and further investigation is warranted into their role as endocrine disrupters in humans.

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Anti‐Androgenic Activity of Fatty Acids

Cited by 45 publications

References 26 publications

The activation of OR51E1 causes growth suppression of human prostate cancer cells

The activation of OR51E1 causes growth suppression of human prostate cancer cells

Combination of unsaturated fatty acids and ionizing radiation on human glioma cells: cellular, biochemical and gene expression analysis

Assessment of hormone-like activities inGinkgo biloba,Elettaria cardamomumandPlantago ovataextracts usingin vitroreceptor-specific bioassays

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