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  • Several of the plant extracts that showed interaction with E


    Several of the plant extracts that showed interaction with ERα and ERβ have differing reports concerning estrogenicity and receptor binding. Extracts of dong quai stimulated MCF-7 proliferation but failed to increase uterine weight or transactivate either ERα or ERβ in a cell assay (Amato et al., 2002). Conflicting results on the estrogenic activity of black cohosh in MCF-7 proliferation assays have been reported (Amato et al., 2002; Bodinet and Freudenstein, 2002; Lau et al., 2005; Liu et al., 2001a, b; Powers and Setzer, 2015; Zierau et al., 2002). There is evidence that the phenolic components in black cohosh have SERM activity (Powers and Setzer, 2015; Seidlova-Wuttke et al., 2003). Reports of varying ER binding activity for saw palmetto and Korean ginseng may be due to differences in extract source, extraction or assay methods (Allkanjari and Vitalone, 2015; Amato et al., 2002; Di Silverio et al., 1992; Elghamry and Hänsel, 1969; Liu et al., 2001a, b). A relatively low binding affinity for ERα and ERβ to dong quai, black cohosh and saw palmetto was observed. Several factors related specifically to plant extracts can contribute to discrepancies in binding assay data reported in the literature. Phytoestrogen production can vary among plant populations (Hloucalová et al., 2016). Extraction methods can eliminate a previously unidentified estrogenic L002 mass from the test mixture or convert natural compounds into active or inactive receptor binding forms. For example, Korean ginseng had insignificant receptor binding in the assay; however, red ginseng, a reddish-brown root obtained by hot water treatment of scraped Korean ginseng roots, had 70 times higher EBE concentration in the ERβ assay (Craker and Simon, 1989; Gray et al., 2016) The literature may not always specify activity based on a concentration/g plant weight, making it difficult to compare results between studies. Early studies examined ER binding of phytoestrogens using uterine or MCF-7 receptor preparations, a cancer cell type in which ERα may be the predominantly expressed receptor (Matsuzaki et al., 1999; Vladusic et al., 2000). Although ERα and ERβ are co-expressed in some tissue types, the occurrence of ERβ isoform can predominate in certain tissue types such as gastrointestinal tract, lung, bladder, vascular endothelium of the endometrium, granulosa cells of the ovary and L002 mass epithelial cells of the prostate (Chakraborty et al., 2012; Critchley et al., 2001; Kuiper et al., 1998; Lecomte et al., 2017a, 2017b; Zhao et al., 2008). Through use of this assay, estrogen receptor binding was detected in some plant extracts not previously identified as estrogenic in the literature. Seed extracts from Queen-Anne’s lace, a common biennial found worldwide, bound weakly to ERα and ERβ in the binding assay. Although no estrogenic activity for this plant has been shown, it has been used for hundreds of years as a morning-after contraceptive and abortifacient and was shown to cause diminished progesterone production in rabbit ovary (Keenan et al., 1997). Compounds from these plants which interact with the ER may have novel structures yet to be identified.
    Declaration of interest
    Steroid hormones exert a pivotal role in the lung [1], [2]. However, only glucocorticoids and their receptors have been extensively studied in lung pathologies, while the impact of sex steroids is partially explored and controversial. Accumulating evidence supports the relevance of sex steroids in lung development, inflammation, and cancer [3]. They affect local synthesis and lung aromatase activity, cell type-specific activity of androgen and estrogen and the detection of sex steroid receptors in normal lung, asthma [4], [5], [6], cystic fibrosis in vivo models [7], [8], [9] and in lung cancer cell lines [3], [10], [11], [12], [13], [14], [15], [16] and tumors [17], [18], [19]. Additionally, in lung cancer, a clear sex difference has been reported, evidenced in prevalence, histological type, mutational burden and prognosis [9], [10], [11], [20], [21]: (i) Women are predominantly affected by adenocarcinomas (ADC), while men by squamous cell carcinomas (SCC); (ii) women survive longer and respond better to treatment, but seem to be more vulnerable to tobacco exposure than men; (iii) lung cancer incidence rates in males are either decreased or stable over the last decade, while an increase is mentioned in females [22]. These data support a potential role of estrogen receptors (ER) in non-small cell lung carcinoma (NSCLC).